(18)

(19)

(20)

(21)

(22)

(23)

(24)

(25)

(27)

(28)

(29)

(30)

(3h

(32)

(33)

BAIR, W.J. Inhalation of radionuclides and carcinogenesis. In: Hanna, M.G.,
Jr., Nettesheim, P., Gilbert, J.R. (Editors). Inhalation Carcinogenesis.
Proceedings of a Biology Division, Oak Ridge National Laboratory Confer-
ence, Gatlinburg, Tennessee, October 8-11, 1969. U.S. Atomic Energy
Commission Symposium Series 18, April 1970, pp. 77-101.

BEAMIS, J.F., Jr., STEIN, A., ANDREWS, J.L., Jr. Changing epidemiology of
lung cancer. Increasing incidence in women. Medical Clinics of North
America 59(2): 315-325, March 1975.

BELCHER, J.R. Adenocarcinoma and smoking. Communications to the
Editor. Chest 67(5):622-623, May 1975.

BENNINGTON, JJ.L., FERGUSON, B.R., CAMPBELL, PB. Epidemiologic
studies of carcinoma of the kidney. II. Association of renal adenoma with
smoking. Cancer 22(4): 821-823, October 1968.

BENNINGTON, J.L., LAUBSCHER, F.A. Epidemiologic studies on carcinoma
of the kidney. I. Association of renal adenocarcinoma with smoking. Cancer
21(6): 1069-1071, June 1968.

BERNARDE, M.A., WEISS, W. A cohort analysis of pancreatic cancer, 1939-
1969. Cancer 393): 1260-1263, March 1977.

BERNFELD, P., HOMBURGER, F., RUSSFIELD, A.B. Strain differences in
the response of inbred Syrian hamsters to cigarette smoke inhalation.
Journal of the National Cancer Institute 53(4). 1141-1157, October 1974.

BERNFELD, P., HOMBURGER, F., SOTO, E., PAI, K.J. Cigarette smoke
inhalation studies in inbred Syrian golden hamsters. Journal of the
National Cancer Institute 63(3): 675-689, September 1979.

BERRY, G., NEWHOUSE, M.L., TUROK, M. Combined effect of asbestos
exposure and smoking on mortality from lung cancer in factory workers.
Lancet 27775): 476-479, September 2, 1972.

BEST, E.W.R. A Canadian Study of Smoking and Health. Ottawa, Depart-
ment of National Health and Welfare, Epidemiology Division, Health
Services Branch, Biostatistics Division, Research and Statistics Directorate,
1966, pp. 65-86.

BEST, E.W.R., JOSIE, G.H., WALKER, C.B. A Canadian study of mortality in
relation to smoking habits: A preliminary report. Canadian Journal of
Public Health 52: 99-106, March 1961.

BLACK, H., ACKERMAN, L.V. The importance of epidermoid carcinoma in
sttu in the histogenesis of carcinoma of the lung. Annals of Surgery 136(1):
44-55, July 1952.

BLOT, W.J., FRAUMENI, J.F., Jr. Geographic patterns of oral cancer in the
United States: Etiologic implications. Journal of Chronic Diseases 30(11):
745-757, November 1977.

BLOT, W.J., MORRIS, L.E., STROUBE, R., TAGNON, L., FRAUMENI, JF.,
Jr. Lung and laryngeal cancers in relation to shipyard employment in
coastal Virginia. Journal of the National Cancer Institute 65(3): 571-575,
September 1980.

BLUMLEIN, H. Zur kausalen Pathogenese des Larynxkarzinome unter
Beriicksichtigung des Tabakrauchens. [Causal pathogenesis of laryngeal
carcinoma with respect to tobacco smoking.] Archiv fiir Hygiene und
Bakteriologie Miinchen 139: 349-404, 1955.

BORLAND, R., HARD, G.C. Early appearance of “transformed” cells from the
kidneys of rats treated with a “single” carcinogenic dose of dimethylnitrosa-
mine (DMN) detected by culture in vitro. European Journal of Cancer 10(3):
177-184, March 1974.

BRADSHAW, E., SCHONLAN D, M. Oesophageal and lung cancers in Natal
African males in relation to certain socio-economic factors. An analysis of
484 interviews. British Journal of Cancer 23(2): 275-284, June 1969.

151
(34)

(35)

(36)

(37)

(38)

(39)

(40)

(41)

(42)

(43)

(44)

(45)

(46)

(47)

(48)

(49)

(50)

152

BRESLOW, L., HOAGLIN, L., RASMUSSEN, G., ABRAMS, H.K. Occupations
and cigarette smoking as factors in lung cancer. American Journal of Public
Health and the Nation’s Health 44(2): 171-181, February 1954.

BRIDGER, G.P., REAY-YOUNG, P. Laryngeal cancer and smoking. Medical
Journal of Australia 2(8): 293-294, August 21, 1976.

BRODERS, A.C. Squamous-cell epithelioma of the lip. A study of five hundred
and thirty-seven cases. Journal of the American Medical Association 74(10):
656-664, March 6, 1920.

BROWNE, R.M., CAMSEY, M.C., WATERHOUSE, J .A.H., MANNING, G.L.
Etiological factors in oral squamous cell carcinoma. Community Dentistry
and Oral Epidemiology 5: 301-306, 2977.

BUCKLEY, J.D., DOLL, R., HARRIS, R.W.C., VESSEY, M.P., WILLIAMS,
P.T. Case control study of the husbands of women with dysplasia or
carcinoma of the cervix uteri. Lancet 8254(ID: 1010-1014, 1981.

CARNES, W.H. The respiratory epithelium of patients with lung cancer. In:
The Morphological Precursors of Cancer. Proceedings of an International
Conference held at the University of Perugia, Italy, June 26-30, 1961, pp.
625-634.

CARNOW, B.W. The “urban factor” and lung cancer: Cigarette smoking or
air pollution? Environmental Health Perspectives 22: 17-21, February 1978.

CEDERLOF, R., DOLL, R., FOWLER, B., FRIBERG, L., NELSON, N., VOUK,
V. (Editors). Air pollution and cancer: Risk assessment methodology and
epidemiological evidence. Report of a task group. Environmental Health
Perspectives 22: 1-12, February 1978.

CEDERLOF, R., FRIBERG, L., HRUBEC, Z., LORICH, U. The Relationship of
Smoking and Some Social Covariables to Mortality and Cancer Morbidity. A
ten year follow-up in a probability sample of 55,000 subjects, age 18-69, Part
1 and Part 2. Stockholm, Sweden, Department of Environmental Hygiene,
The Karolinska Institute, 1975, pp. 1-91.

CEDERLOF, R., FRIBERG, L., LUNDMAN, T. The interactions of smoking,
environment and heredity and their implications for disease etiology. A
report of epidemiological studies on the Swedish Twin Registries. Acta
Medica Scandinavica. Supplementum 612: 1-128, September 1977.

CHODYNICKI, S., GINDZIENSKA, E., TUPALSKA, M., HASSMANN, E.
Epidemiological characteristics of patients with laryngeal cancer and
precancerous conditions. Otolaryngologia Polska 34(4): 377-382, 1980.

CLAYSON, D.B. Occupational bladder cancer. Preventive Medicine 5(2): 228-
244, June 1976. (Abstract)

COBB, B.G., ANSELL, J.S. Cigarette smoking and cancer of the bladder.
Journal of the American Medical Association 1935): 329-332, August 2,
1965.

COLE, P. Cancer and occupation: Status and needs of epidemiolgoic research.
Cancer 39(40): 1788-1791, April 1977.

COLE, P., MONSON, R.R., HANING, H., FRIEDELL, G.H. Smoking and
cancer of the lower urinary tract. New England Journal of Medicine 284(3):
129-134, January 21, 1971.

CORNFIELD, J. A method of estimating comparative rates from clinical data.
Applications to cancer of the lung, breast, and cervix. Journal of the
National Cancer Institute 11: 1269--1275, 1951.

CRONINGER, A.B., GRAHAM, E.A., WYNDER, ELL. Experimental produc-
tion of carcinoma with tobacco products. V. Carcinoma induction in mice
with cigar, pipe, and all-tobacco cigarette tar. Cancer Research 18(11): 1263~
1271, December 1958.
(51)

(52)

(53)

(54)

(85)

(56)

(57)
(58)

(59)

(60)

(61)

(62)

(64)

(65)

(66)

(67)

(68)

(69)

(70)

CUNNINGHAM, G.J., WINSTANLEY, D.P. Hyperplasia and metaplasia in
the bronchial epithelium. Annals of the Royal College of Surgeons of
England 24(5): 323-330, May 1959.

DALY, C.J., STRONG, E.W. Carcinoma of the glottic larynx. American
Journal of Surgery 130(4): 489-492, 1975.

DAVIES, R.F., DAY, T.D. A study of the comparative carcinogenicity of
cigarette and cigar smoke condensate on mouse skin. British Journal of
Cancer 23(2): 363-368, June 1969.

DEANER, R.M., TRUMMER, M.J. Carcinoma of the lung in women. Journal
of Thoracic and Cardiovascular Surgery 59(4): 551-554, April 1970.

DEELEY, T.J., COHEN, S.L. The relationship between cancer of the bladder
and smoking. In: Bladder Cancer. Proceedings of the 5th Inter-American
Conference on Toxicology and Occupational Medicine, Coral Gables, Florida,
University of Miami, School of Medicine, 1967, pp. 163-169.

DEVINE, K.D. Pathologic effects of smoking on the larynx and oral cavity.
Proceedings of the Mayo Clinic 35(13): 349-352, June 22, 1960.

DOLL, R. Etiology of lung cancer. Advances in Cancer Research 3: 1-50, 1955.

DOLL, R. Strategy for detection of cancer hazards to man. Nature 265(5595):
389-596, February 17, 1977.

DOLL, R. Atmospheric pollution and lung cancer. Environmental Health
Perspectives 22: 23-31, February 1978.

DOLL, R., GRAY, R., HAFNER, B., PETO, R. Mortality in relation to
smoking: 22 years’ observations on female British doctors. British Medical
Journal 2806219): 967-971, April 5, 1980.

DOLL, R., HILL, A.B. A study of the aetiology of carcinoma of the lung.
British Medical Journal 2: 1271-1286, December 13, 1952.

DOLL, R., HILL, A.B. The mortality of doctors in relation to their smoking
habits; a preliminary report. British Medical Journal 1(4877): 1451-1455,
June 26, 1954.

DOLL, R., HILL, A.B. Lung cancer and other causes of death in relation to
smoking. A second report on the mortality of British doctors. British
Medical Journal 2: 1071-1081, 1956.

DOLL, R., HILL, A.B. Mortality in relation to smoking: Ten years’ observa-
tions of British doctors (Part 1). British Medical Journal 1(5395): 1399-1410,
May 30, 1964.

DOLL, R., HILL, A.B. Mortality in relation to smoking: Ten years’ observa-
tions of British doctors. Concluded. British Medical Journal 1(5396): 1460-
1467, June 6, 1964.

DOLL, R., HILL, A.B. Mortality of British doctors in relation to smoking:
Observations on coronary thrombosis. In: Haenzel, W. (Editor). Epidemiolog-
ical Approaches to the Study of Cancer and Other Chronic Diseases. National
Cancer Institute Monograph No. 19. U.S. Department of Health, Education,
and Welfare, Public Health Service, National Cancer Institute, January
1966, pp. 205-268.

DOLL, R., HILL, A.B., KREYBERG, L. The significance of cell type in relation
to the aetiology of lung cancer. British Journal of Cancer II: 43-48, 1957.

DOLL, R., PETO, R. Mortality in relation to smoking: 20 years’ observations
on male British doctors. British Medical Journal 2(6051): 1525-1536,
December 25, 1976.

DOLL, R., PETO, R. Mortality among doctors in different occupations. British
Medical Journal 1(6074): 1433-1436, June 4, 1977.

DOLL, R., PETO, R. The causes of cancer: Quantitative estimates of avoidable
risks of cancer in the United States today. Journal of the National Cancer
Institute 66(6): 1191-1308, June 1981.

153
(72)

(72)

(73)

(74)

(75)

(76)

(77)

(78)

(79)

(80)

(81)

(82)

(83)

(84)

(86)

154

DOLL, R., PIKE, M.C. Trends in mortality among British doctors in relation
to their smoking habits. Journal of the Royal College of Physicians 6(2): 216-
222, January 1972.

DONTENWILL, W., CHEVALIER, H.-J., HARKE, H-P., KLIMISCH, H.-J.,
KUHNIGK, C., RECKZEH, G., SCHN EIDER, B. Untersuchungen iiber den
Effekt der chronischen Zigarettenrauchinhalation beim Syrischen Gold-
hamster und iiber die Bedeutung des Vitamin A auf die bei Berauchung
gefunden Organveranderungen. [Studies on the effect of chronic cigarette
smoke inhalation in Syrian golden hamsters and the importance of Vitamin
A on morphological alterations after smoke exposure.] Zeitschrift fir
Krebsforschung und Klinische Onkologie 89(2): 153-180, 1977.

DONTENWILL, W., CHEVALIER, H.-J., HARKE, H.-P., LAFRENZ, U.,
RECKZEH, G., SCHNEIDER, B. Investigations on the effects of chronic
cigarette-smoke inhalation in Syrian golden hamsters. Journal of the
National Cancer Institute 51(6):1781-1832, December 1973.

DORN, H.F. The mortality of smokers and nonsmokers. Proceedings of the
Social Statistics Section of the American Statistical Association. Papers
presented at the Annual Meeting of the American Statistical Association,
Chicago, Illinois, December 27-30, 1958. Washington, D.C., American
Statistical Association, 1959, pp. 3471.

DUNHAM, L.J., RABSON, A.S., STEWART, HLL., FRANK, A.S., YOUNG,
J.L., Jr. Rates, interview, and pathology study of cancer of the urinary
bladder in New Orleans, Louisiana. Journal of the National Cancer Institute
41(3): 683-709, September 1968.

DUNN, J.E., LINDEN, G., BRESLOW, L. Lung cancer mortality experience of
men in certain occupations in California. American Journal of Public
Health 50(10): 1475-1487, October 1960.

DUTTA-CHOUDHURI, R., ROY, H., SEN GUPTA, B.K. Cancer of the larynx
and hypopharynx. A clinicopathological study with special reference to
aetiology. Journal of the Indian Medical Association 32(9): 352-362, May 1,
1959.

ENSTROM, J.E. Cancer mortality among low-risk population. CA—A Cancer
Journal for Clinicians 29(6): 352-361, November-December 1979.

ENSTROM, J.E. Cancer mortality among Mormons in California during
1968-1975. Journal of the National Cancer Institute 65(5): 1073-1082,
November 1980.

EVANS, A.S. 1976. Causation and disease: The Henle-Koch postulates
revisited. Yale Journal of Biology and Medicine 49(2): 175-195, May 1976.

FEDERAL TRADE COMMISSION. Report of “Tar,” Nicotine and Carbon
Monoxide of the Smoke of 200 Varieties of Cigarettes. Washington, D.C.,
Federal Trade Commission, December 1981. /

FISHER, R.A. Danger of cigarette smoking. British Medical Journal 2: 297-
298, 1957. (Letter to the Editor).

FISHER, R.A. Smoking, the Cancer Controversy. Same Attempts to Assess the
Evidence. Oliver and Boyd, Edinburgh, 1959, 47 pp.

FLAMM, H., KUNZE, M., KUNZE, MJ. Tumoren der Harnblase und
Zigarettenrauchen. (Tumors of the urinary bladder and cigarette smoking.]
Osterreichisches Bundesinstitut fur Gesundheitswesen, Vienna, 1975.

FLANDERS, W.D., ROTHMAN, K.J. Interaction of alcohol and tobacco in
laryngeal cancer. American Journal of Epidemiology, in press.

GARFINKEL, L. Cancer mortality in nonsmokers: Prospective study by the
American Cancer Society. Journal of the National Cancer Institute 65(5):
1169-1173, November 1980.
(87)

(88)

(89)

(90)

(91)

(92)

(93)

(94)

(95)

(96)

(97)

(98)

(99)

(100)

(101)

(102)

(103)

377-

GELFAND, M., GRAHAM, A.J.P., LIGHTMAN, S. Carcinoma of bronchus
and the smoking habit in Rhodesian Africans. British Medical Journal
3(5616): 468-469, August 24, 1968.

GRAHAM, S., DAYAL, H., ROHRER, T., SWANSON, M., SULTZ, H.,
SHEDD, D., FISCHMAN, S. Dentition, diet, tobacco, and alcohol in the
epidemiology of oral cancer. Journal of the National Cancer Institute 59(6):
1611-1618, December 1977.

GRAY, S.H. CORDONNIER, J. Early carcinoma of the lung. A. M. A. Archives
of Surgery 19: 1618-1626, 1929.

GSELL, O. Carcinome bronchique et tabac. [Bronchial carcinoma and
tobacco.] Medecine et Hygeine 12(279): 429-431, December 1, 1954.

HAENSZEL, W., KURIHARA, M., LOCKE, F.B., SHIMUZU, K., SEGI, M.
Stomach cancer in Japan. Journal of the National Cancer Institute 56(2):
265-274, February 1976.

HAENSZEL, W., KURIHARA, M., SEGI, M., LEE, R.K.C. Stomach cancer
among Japanese in Hawaii. Journal of the National Cancer Institute 49:
969-988, 1972.

HAENSZEL, W., LOVELAND, D.B., SIRKEN, M.G. Lung-cancer mortality as
related to residence and smoking histories. I. White males. Journal of the
National Cancer Institute 28(4): 947-1001, April 1962.

HAENSZEL, W., SHIMKIN, M.B. A retrospective study of lung cancer in
women. Journal of the National Cancer Institute 21(5): 825-842, November
, 1958.

HAENSZEL, W., TAEUBER, K.E. Lung-cancer mortality as related to
residence and smoking histories. II. White females Journal of the National
Cancer Institute 32(4): 803-838, April 1964.

HAMILTON, J.D., BROWN, T.C., MacDONALD, F.W. Morphological changes
in smokers’ lungs. Canadian Medical Association Journal 77(3): 177-182,
August 1, 1957.

HAMMOND, E.C. Evidence on the effects of giving up cigarette smoking.
American Journal of Public Health 55(5): 682-691, May 1965.

HAMMOND, E.C. Smoking in relation to the death rates of one million men
and women. In: Haenszel, W. (Editor). Epidemiological Approaches to the
Study of Cancer and Other Chronic Diseases. National Cancer Institute
Monograph No. 19. U.S. Department of Health, Education, and Welfare,
Public Health Service, National Cancer Institute, January 1966, pp. 127-
204,

HAMMOND, E.C. Smoking habits and air pollution in relation to lung cancer.
In: Lee, D.H.K. (Editor). Environmental Factors in Respiratory Disease.
Fogarty International Center Proceedings No. 11, New York, Academic
Press, 1972, pp. 177-198.

HAMMOND, E.C., GARFINKEL, L. Coronary heart disease, stroke, and
aortic aneurysm. Factors in the etiology. Archives of Environmental Health
19(2): 167-182, August 1969.

HAMMOND, E.C., GARFINKEL, L. General air pollution and cancer in the
United States. Preventive Medicine 2): 206-211, March 1980.

HAMMOND, E.C., GARFINKEL, L., SEIDMAN, H., LEW, E.A. “Tar” and
nicotine content of cigarette smoke in relation to death rates. Environmen-
tal Research 12(3): 263-274, December 1976.

HAMMOND, E.C., GARFINKEL, L., SEIDMAN, H., LEW, E.A. Some recent
findings concerning cigarette smoking. In: Hiatt, H.H., Watson, J.D.,
Winsten, J.A. (Editors). Origins of Human Cancer. Book A: Incidence of
Cancer in Humans. Cold Spring Harbor Conference on Cell Proliferation,
Volume 4. Cold Spring Harbor, New York, Cold Spring Harbor Laboratory,
1977, pp. 101-112.

155

310 0 - 82 - 12
(104)

(105)

(106)

(107)

(108)

(109)

(110)

(111)

(112)

(113)

(114)

(115)

(116)

(117

(118)

156

HAMMOND, E.C., HORN, D. Smoking and death rates—Report on forty-four
months of follow-up on 187,783 men. I. Total mortality. Journal of the
American Medical Association 166(10): 1159-1172, March 8, 1958.

HAMMOND, E.C., HORN, D. Smoking and death rates—Report on forty-four
months of follow-up of 187,783 men. II. Death rates by cause. Journal of the
American Medical Association 166(11): 1294-1308, March 15, 1958.

HAMMOND, E.C., SEIDMAN, H. Smoking and cancer in the United States.
Preventive Medicine 9(2): 169-173, March 1980.

HAMMOND, E.C., SELIKOFF, LJ. Relation of cigarette smoking to risk of
death of asbestos-associated disease among insulation workers in the United
States. In: Bogovski P., Gilson, J.C., Timbrell, V., Wagner, J.C., Davis, W.
(Editors). Biological Effects of Asbestos. International Agency for Research
on Cancer, Scientific Publication No. 8, Lyon, France, International Agency
for Research on Cancer, 1973, pp. 312-317.

HARRIS, R.W.C., BRINTON, L.A., COWDELL, R.H., SKEGG, D.C.T., SMITH,
P.G., VESSEY, M.P., DOLL, R. Characteristics of women with dysplasia or
carcinoma in situ of the cervix uteri. British Journal of Cancer 42(359): 359-
369, 1980.

HIGGINSON, J. Present trends in cancer epidemiology. In: Morgan, J.F.
(Editor). Proceedings of the Eighth Canadian Cancer Conference Honey
Harbour, Ontario, Canada, 1968. Elmsford, New York, Pergamon Press,
1969, pp. 43-75.

HIGGINSON, J. A hazardous society? Individual versus community responsi-
bility in cancer prevention. American Journal of Public Health 66(4): 359-
366, April 1976.

HIGGINSON, J., JENSEN, O.M. Epidemiological review of lung cancer in
man. In: Mohr, E., Schmaehl, D., Tomatis, L. (Editors). Air Pollution and
Cancer in» Man. International Agency for Research on Cancer, Scientific
Publication No. 16, Lyon, France, International Agency for Research on
Cancer, 1977, pp. 169-189. .

HILL, A.B. The Environment and Disease: Association or Causation? Proceed-
ings of the Royal Society of Medicine, 58(5): 295-300, May 1965.

HINDS, M.W., KOLONEL, L.N., LEE, J., HIROHATA, T. Association between
cancer incidence and alcohol/cigarette consumption among five ethnic
groups in Hawaii. British Journal of Cancer 41(6): 929-940, June 1980.

HINDS, M.W., THOMAS, D.B., O'REILLY, HP. Asbestos, dental x-rays,
tobacco, and alcohol in the epidemiology of laryngeal cancer. Cancer 44(3):
1114-1120, September 1979.

HIRAYAMA, T. Smoking in Relation to the Death Rates of 265,118 Men and
Women in Japan. Tokyo, National Cancer Center, Research Institute,
Epidemiology Division, September 1967, 14 pp.

HIRAYAMA, T. Smoking and drinking—Is there a connection? Smoke
Signals 16(7): 1-8, July 1970.

HIRAYAMA, T. Smoking in Relation to the Death Rates of 265,118 Men and
Women in Japan. A Report on 5 Years of Follow-up. Presented at the
American Cancer Society’s 14th Science Writers’ Seminar, Clearwater
Beach, Florida, March 24-29, 1972, 15 pp.

HIRAYAMA, T. Operational aspects of cancer public education in Japan. In:
Summary Proceedings of the International Conference on Public Education
About Cancer. UICC Technical Report Series, Volume 18, Geneva, 1975, pp.
85-90.
(119)

(120)

(121)

(122)

(123)

(124)

(125)

(126)

(127)

(228)

(129)

(130)

(131)

(132)

HIRAYAMA, T. Prospective studies on cancer epidemiology based on census
population in Japan. In: Bucalossi, P., Veronesi, U., Cascinelli, N. (Editors).
Cancer Epidemiology, Environmental Factors. Volume 3. Proceedings of the
11th International Cancer Congress, Florence, Italy, October 20-26, 1974.
Amsterdam, Excerpta Medica, 1975, pp. 26-35.

HIRAYAMA, T. Changing patterns of cancer in Japan with special reference
to the decrease in stomach cancer mortality. In: Hiatt, H.H., Watson, J.D.,
Winsten, J.A. (Editors). Origins of Human Cancer. Book A: Incidence of
Cancer in Humans. Cold Spring Harbor Conference on Cell Proliferation,
Volume 4. Cold Spring Harbor, New York, Cold Spring Harbor Laboratory,
1977, pp. 55-75.

HITOSUGI, M. Epidemiological study of lung cancer with special reference to
the effect of air pollution and smoking habit. Bulletin of the Institute of
Public Health 17(3): 237-256, September 1968.

HOEY, J.. MONTOERNAY, C., LAMBERT, R. Wine and tobacco: Risk factors
for gastric cancer in France. American Journal of Epidemiology 113(6): 668-
674, June 1981.

HOFFMANN, D., WYNDER, E.L. Environmental respiratory carcinogenesis.
In: Searle, C.E. (Editor). Chemical Carcinogens. American Chemical Society
Monograph 173. Washington, D.C., American Chemical Society, 1970, 324—
365 pp.

HOLLAND, J.F., FREI, E. II. Cancer Medicine. Lea and Febiger, Philadel-
phia, 1974, pp. 1438, 1797.

HOMBURGER, F. “Smokers’ Larynx” and carcinoma of the larynx in Syrian
hamsters exposed to cigarette smoke. Laryngoscope 85(11, Part 1): 1874-
1881, November, 1975.

HOMBURGER, F., SOTO, H., ALTHOFF, J.. DALQUEN, P., HEITZ, P.
Carcinoma of the larynx in hamsters exposed to cigarette smoke. American
Journal of Pathology 95: 845-848, June 1979.

HOMBURGER, F., TREGER, A., BAKER, J.R. Mouse-skin painting with
smoke condensates from cigarettes made of pipe, cigar, and cigarette
tobacco. Journal of the National Cancer Institute 31(6): 1445-1459, Decem-
ber 1963.

HOOVER, R., COLE, P. Population trends in cigarette smoking and bladder
cancer. American Journal of Epidemiology 94(5): 409-418, November 1971.

HOWE, G.R., BURCH, J.D., MILLER, A.B., COOK, G.M., ESTEVE, J.,
MORRISON, B., GORDON, P., CHAMBERS, L.W., FODOR, G., WINSOR,
G.M. Tobacco use, occupation, coffee, various nutrients, and bladder cancer.
Journal of the National Cancer Institute 64(4):701-713, April 1980.

JASMIN, G., CHA, J.W. Renal adenomas induced in rats by dimethylnitrosa-
mine. An electron microscopic study. Archives of Pathology 87(3): 267,
March 1969.

KAHN, H.A. The Dorn study of smoking and mortality among U.S. veterans:
Report on eight and one-half years of observation. In: Haenszel, W. (Editor).
Epidemiological Approaches to the Study of Cancer and Other Chronic
Diseases. National Cancer Institute Monograph No. 19., U.S. Department of
Health, Education, and Welfare, Public Health Service, National Cancer
Institute, January 1966, pp. 1-125. .

KAMIONKOWSKI, M.D., FLESHLER, B. The role of alcoholic intake in
esophageal carcinoma. American Journal of the Medical Sciences 249(6):
696-700, June 1965.

157
(133)

(134)

(135)

(136)

(137)

(138)

(139)

(140)

(141)

(142)

(143)

(144)

(145)

(146)

(147)

(148)

(149)

158

KARBE, E., KOSTER, K. Carcinogenicity of inhaled cigarette smoke in the
NMU-pretreated hamster larynx. In: Karbe, E., Park, JF. (Editors).
Experimental Lung Cancer: Carcinogenesis and Bioassays. International
Symposium, Seattle, Washington, June 23-26, 1974. New York, Springer-
Verlag, 1974, pp. 369-382.

KASPERSKI, A. Occurrence of laryngeal carcinoma in Bydogszcez County
(1955-75) with regard to some epidemiological factors. Otolaryngologia
Polska 34(1): 125-126, 1980.

KELLER, A.Z. Cirrhosis of the liver, alcoholism and heavy smoking associ-
ated with cancer of the mouth and pharynx. Cancer 206): 1015-1022, June
1967.

KELLER, A.Z., TERRIS, M. The association of alcohol and tobacco with
cancer of the mouth and pharynx. American Journal of Public Health
55(10): 1578-1585, October 1965.

KENNEDY, A. Relationship between cigarette smoking and histological type
of lung cancer in women. Thorax 28(2): 204-208, March 1973.

KENSLER, C.J. The pharmacology of tobacco smoke effects of chronic
exposure. In: James, G., Rosenthal, T. (Editors). Tobacco and Health.
Springfield, Illinois, Charles C. Thomas, 1962, pp. 5-20.

KERR, W.K., BARKIN, M., LEVERS, P.E., WOO, S.K.-C., MENCZYK, Z. The
effect of cigarette smoking on bladder carcinogens in man. Canadian
Medical Association Journal 93( 1): 1-7, July 3, 1965.

KESSLER, IL, KULCAR, Z., ZIMOLO, A., GRGUREVIC, M. STRNAD, M.,
GOODWIN, B.J. Cervical cancer in Yugoslavia. II. Epidemiologic factors of
possible etiologic significance. Journal of the National Cancer Institute 53(1):
51-60, July 1974.

KIDA, H., OMOTO, T., SAKAMOTO, K. MOMOSE, S. Fukuoka ken hokubu
ni okeru boko shuyo no ekigaku to tokei. [Statistical and epidemiological
studies on tumor of the urinary bladder in the northern parts of Fukuoka
Prefecture.] Hifu to Hinyo 30(5): 883-889, October 1968.

KIRIKAE, I. Epidemiology of cancer of the larynx. Japanese Journal of
Clinical Medicine 26(8): 1808-181 1, August 1968.

KISSIN, B., KALEY, M.M., SU, W.H., LERNER, R. Head and neck cancer in
alcoholics. The relationship to drinking, smoking, and dietary patterns.
Journal of the American Medical Association 224(8): 1174-1175, May 21,
1973.

KNUDTSON, K.P. The pathologic effects of smoking tobacco on the trachea
and bronchial mucosa. American Journal of Clinical Pathology 33(4): 310-
317, April 1960.

KONTUREK, S.J., DALE, J., JACOBSON, E.D., JOHNSON, L.R. Mechanisms
of nicotine-induced inhibition of pancreatic secretion of bicarbonate in the
dog. Gastroenterology 62(3): 425-429, March 1972.

KOTIN, P., FALK, H.L. Polluted urban air and related environmental factors
in the pathogenesis of pulmonary cancer. Diseases of the Chest 45(3): 236—
246, March 1964. .

KOULUMIES, M. Smoking and pulmonary carcinoma. Acta Radiologica 39:
255-260, 1953.

KREYBERG, L. Histological lung cancer types: A morphological and biologi-
cal correlation. Acta pathologica et Microbiologica Scandinavica. (Supple-
mentum 152), 1962, 92 pp. .

KUNZE, M., VUTUC, C. Threshold of tar exposure: Analysis of smoking
history of male lung cancer cases and controls. In: Gori, G.B., Bock, F.G.
(Editors). Banbury Report 3—A safe cigarette? Cold Spring Harbor, New
York, Cold Spring Harbor Laboratory, March 12, 1980, pp. 29-36.
(150)

(15D
(152)

(153)

(154)
(155)

(155a)

(156)

(157)

(158)

(159)
(160)
(161)
(162)
(163)
(164
(165)

(166)

KURATSUNE, M., KOHCHI, S., HORIE, A. Carcinogenesis in the esophagus.
I. Penetration of benzo(a)pyrene and other hydrocarbons into the esophageal
mucosa. Gann 56(2): 177-187, April 1965.

KURITA, H. Clinico-epidemiological study of stomach cancer considering sex
and age differences. Japan Journal of Cancer Clinics 20(8): 580-593, 1974.

LANCASTER, H.O. Cancer statistics in Australia. Part II. Respiratory
system. Medical Journal of Australia 1: 1006-1011, June 30, 1962.

LEE, B.K., MURPHY, G. Determination of arsenic content of American
cigarettes by neutron activation analysis. Cancer 23(6): 1315-1317, June
1969.

LEE, P.N. (Editor). Tobacco Consumption in Various Countries. Research
Paper No. 6, 4th Edition. London, Tobacco Research Council, 1975, 86 pp.

LEE, P.N., GARFINKEL, L. Mortality and type of cigarette smoked. Journal
of Epidemiology and Community Health 35(1): 16-22, March 1981.

LEVIN, M.L., GOLDSTEIN, H., GERHARDT, P.R. Cancer and tobacco
smoking. A preliminary report. Journal of the American Medical Associa-
tion 143(4): 336-338, May 27, 1950.

LICKINT, F. Der Tabakrauch als Ursache des Lungenkrebses. Spezieller Teil
IV. Atiologie und Prophylaxe des Lungenkrebses. [Tobacco smoke as cause
of lung cancer. Special Section IV. In: Etiology and Prophylaxis of Lung
Cancer.] Dresden, Theodor Steinkopff, 1953, pp. 76-102.

LILIENFELD, A.M., LEVIN, M.L., MOORE, G.E. The association of smoking
with cancer of the urinary bladder in humans. American Medical Associa-
tion Archives of Internal Medicine 98: 129-135, 1956.

LILIENFELD, A.M., LILIENFELD, D.E. Foundations of Epidemiology. 2nd
Edition, New York, Oxford University Press, 1980.

LOCKWOOD, K. On the etiology of bladder tumors in Kobenhavn-Frederiks-
berg. An inquiry of 369 patients and 369 controls. Acta Pathologica et
Microbiologica Scandinavica 51(Supplementum 145): 1-166, 1961.

LOMBARD, H.L., DOERING, C.R. Classics in oncology. Cancer studies in
Massachusetts. 2. Habits, characteristics and environment of individuals
with and without cancer. New England Journal of Medicine 198: 481-487,
1928.

LOMBARD, H.L., SNEGIREFF, L.S. An epidemiological study of lung cancer.
Cancer 12(2): 406-413, March-April 1959.

LONGNECKER, D.S., SHINOZUKA, H., DEKKER, A. Focal acinar cell
dysplasia in human pancreas. Cancer 45(3): 534-540, February 1, 1980.

LUNDIN, F.E., Jr., LLOYD, J.W., SMITH, E.M., ARCHER, V.E., HOLADAY,
D.A. Mortality of uranium miners in relation to radiation exposure, hard-
rock mining and cigarette smoking-—1950 through September 1967. Health
Physics 16(5): 571-578, May 1969.

LYON, J.L., GARDNER, J.W., WEST, D.W. Cancer in Utah: Risk by religion
and place of residence. Journal of the National Cancer Institute 65(5): 1063-
1071, November 1980.

LYON, J.L., GARDNER, J.W., WEST, D.W. Cancer incidence in Mormons and
Non-Mormons in Utah during 1967-1975. Journal of the National Cancer
Institute 65): 1055-1061, November 1980. .

LYON, J.L., GARDNER, J.W., WEST, D.W. Cancer risk and life-style: Cancer
among Mormons from 1967-1975. In: Cairns, J., Lyon, J.L., Skolnick, M.
(Editors). Cancer Incidence in Defined Populations. Banbury Report No. 4,
Cold Spring Harbor, New York, Cold Spring Harbor Laboratory, 1980, pp. 3-
30.

159
(167)

(168)

(169)

(170)

(171)

(172)

(173)

(174)

(178)

(176)

177)

(178)

(179)

(180)

(181)

(182)

(183)

160

MacDONALD, LG. Statement of Ian G. MacDonald, University of Southern
California. In: Hearings Before the Legal and Monetary Subcommittee of the
Committee on Government Operations: False and Misleading Advertising
(Filter-Tip Cigarettes). July 18, 19, 23-26, 1957, U.S. House of Representa-
tives. Government Printing Office, 1957, pp. 34-61.

MacMAHON, B., PUGH, T. Epidemiology: Principles, and Methods. Boston,
Little Brown and Company, 1970, pp. 17-27.

MacMAHON, B., YEN, S, TRICHOPOULOS, D., WARREN, K., NARDI, G.
Coffee and cancer of the pancreas. New England Journal of Medicine
304(11): 630-633, 1981.

MAKHYOUN, N.A. Smoking and bladder cancer in Egypt. British Journal of
Cancer 30(6): 577-581, December 1974.

MALTONI, C., CARRETTI, D., CANEPARI, C., GHETTI, G. Incidenza della
metaplasia squamosa dell’epitelio respiratorio in rapporto al fumo di
sigaretta. Studio citologico su 1000 individui di sesso machile apparente-
mente sani. [Incidence of squamous metaplasia of the respiratory epithelium
in relation to cigarette smoking. Cytological study on 1000 apparently
healthy male individuals.] Cancro 21(4): 349-356, 1968.

MARTINEZ, I. Factors associated with cancer of the esophagus, mouth and
pharynx in Puerto Rico. Journal of the National Cancer Institute 42(6):
1069-1094, June 1969.

MARTINEZ, I. Retrospective and prospective study of carcinoma of the
esophagus, mouth, and pharynx in Puerto Rico. Boletin de la Asociacion
Medica de Puerto Rico 62(6): 170-178, June 1970.

MARTISCHNIG, K.M., NEWELL, D.J., BARNSLEY, W.C., COWAN, W.K.,
FEINMANN, E.L., OLIVER, E. Unsuspected exposure to asbestos and
bronchogenic carcinoma. British Medical Journal 1(6063): 746-749, March
19, 1977.

MASON, T.J., McKAY, F.W., HOOVER, R., BLOT, W.J., FRAUMENI, J.F.
Atlas of Cancer Mortality for U.S. Counties. 1950-1969. Washington, D.C.,
Government Printing Office, DHEW Publication No. (NIH)75-780, 1975.

MATTHEWS, M.J., GORDON, P.R. Morphology of pulmonary and pleural
malignancies. In: Straus, MJ. (Editor). Lung Cancer Diagnosis and Treat-
ment. New York, Grune and Stratton, 1977.

MAXWELL, J.C., Jr. Trends in cigarette consumption. In: Gori, G.B., Bock,
F.G. (Editors). Banbury Report 3—A Safe Cigarette? Cold Spring Harbor,
New York, Cold Spring Harbor Laboratory, March 12, 1980, pp. 325-332.

McCONNELL, R.B., GORDON , K.C.T., JONES, T. Occupational and personal
factors in the aetiology of carcinoma of the lung. Lancet 2: 651-656, October
4, 1952.

McLOY, D.G., HECHT, S.S., WYNDER, E.L. The roles of tobacco, alcohol, and
diet in the etiology of upper alimentary and respiratory tract cancers.
Preventive Medicine 5): 622-629, September 1980.

MEHTA, FS., PINDBORG, J.J., BHONSLE, R.B., SINOR, P.N. Incidence of
oral leucoplakias among 20,358 Indian villagers in a 7-year period. British
Journal of Cancer 33(5): 549-554, May 1976.

MILLS, C.A., PORTER, M.M. Tobacco smoking habits and cancer of the
mouth and respiratory system. Cancer Research 10: 539-542, 1950.

MILLS, C.A., PORTER, M.M. Tobacco smoking, motor exhaust fumes, and
general air pollution in relation to lung cancer incidence. Cancer Research
17: 981-990, 1957.

MONSON, R.R., LYONS, J.L. Proportional mortality among alcoholics.
Cancer 36(3): 1077-1079, September 1975.
(184)

(185)

(186)

(187)

(188)

(189)

(190)

(191)

(192)

(193)

(194)

(195)

(196)

(197)

MONTESANO, R., SAFFIOTTI, U., SHUBIK, P. The role of topical and
systemic factors in experimental respiratory carcinogenesis. In: Hanna,
M.G., Jr., Nettesheim, P., Gilbert, J.R. (Editors). Inhalation Carcinogenesis.
Proceedings of a Biology Division, Oak Ridge National Laboratory Confer-
ence, Gatlinburg, Tennessee, October 8-11, 1969. Atomic Energy Commis-
sion, Division of Technical Information, AEC Symposium Series No. 18,
April 1970, pp. 353-371.

MOOLGAVKAR, S.H., STEVENS, R.G. Smoking and cancers of bladder and
pancreas: Risk and temporal trends. Journal of the National Cancer
Institute 67(1): 15-23, July 1981.

MOORE, G.E., BISSINGER, L.L., PROEHL, E.C. Intraoral cancer and the use
of chewing tobacco. Journal of the American Geriatrics Society 1: 497-506,
1953.

MORGAN, R.G.H., WORMSLEY, K.G. Progress report: Cancer of the
pancreas. Gut 18(7): 580-596, July 1977.

MORGAN, R.W., JAIN, M.G. Bladder cancer—Smoking, beverages and
artificial sweenteners. Canadian Medical Association Journal III(10): 1067—
1070, November 16, 1974.

MOROSCO, G.J.. GOORINGER, G.C. Lifestyle factors and cancer of the
pancreas: A hypothetical mechanism. Medical Hypothesis 6(9): 971-985,
September 1980.

MUELLER, K.M., KROHN, B.R. Smoking habits and their relationship to
precancerous lesions of the larynx. Journal of Cancer Research and Clinical
Oncology 96(2): 211-217, 1980.

MULLER, F.H. Tabakmissbrauch und Lungencarcinom. [Tobacco abuse and
carcinoma of the lung.] Zeitschrift fiir Krebsforschung 491): 57-84, June
1939.

NAGUIB, S.M., LUNDIN, F.E., Jr. DAVID, HJ. Relation of various
epidemiologic factors to cervical cancer as determined by a screening
program. Obstetrics and Gynecology 284): 451-459, October 1966.

NASIELL, M. The Epithelial Picture in the Bronchial Mucosa in Chronic
Inflammatory and Neoplastic Lung Disease and its Relation to Smoking. A
Comparative Histologic and Sputum-cytologic Study. Stockholm, Cytology
Laboratory, Department of Pathology at Sabbatsberg Hospital, Karolinska
Institutet, 1968, 72 pp.

NATIONAL CANCER INSTITUTE. End Results in Cancer. Report No. 4.,
U.S. Department of Health, Education, and Welfare, Public Health Service,
National Institutes of Health, National Cancer Institute. DHEW Publica-
tion No. (NIH)73-272, 1972, pp. 43-46, 81-84.

NATIONAL CANCER INSTITUTE. Cancer Patient Survival. Report No. 5,
U.S. Department of Health Education and Welfare, Public Health Service,
National Institutes of Health, National Cancer Institute. DHEW Publica-
tion No. (NIH)77-922, 1976, pp. 11-55.

NATIONAL CANCER INSTITUTE, NATIONAL INSTITUTE OF ENVIRON-
MENTAL HEALTH SCIENCES, NATIONAL INSTITUTE FOR OCCUPA-
TION SAFETY AND HEALTH. Estimates of the Fraction of Cancer in the
United States Related to Occupational Factors. U.S. Department of Health,
Education, and Welfare, Public Health Service, National Institutes of
Health, National Cancer Institute, September 15, 1978, pp. 1-50.

NATIONAL CANCER INSTITUTE. Surveillance Epidemiology End Results.
Incidence and mortality data: 1973-1977. National Cancer Institute Mono-
graph No.57,U.S. Department of Health and Human Services, Public Health
Service, National Institutes of Health, National Cancer Institute, 1981, 1082
pp.

161
(198)

(199)

(200)

(201)

(202)

(203)

(204)

(205)

(206)

(207)

(208)

(209)

(210)

(211)

(212)

(213)

(214)

(215)

162

NATIONAL CANCER INSTITUTE. Cancer Mortality in the United States,
1950-1977. In: McKay, F.W., Hanson, M.R., Miller, R.WiAuthors). Journal
of the National Cancer Institute. Monograph No. 59, April 1982, 475 pp.

NATIONAL CENTER FOR HEALTH STATISTICS. Provisional statistics.
Annual survey for the United States, 1980. Monthly Vital Statistics Report.
Volume 29, No. 18, DHHS Publication No. (PHS)81-1120, September 17,
1981.

NATIONAL CENTER FOR HEALTH STATISTICS. Mortality From Diseases
Associated With Smoking: United States 1960-77. Vital and Health Statis-
tics, Series 20, No. 17, DHHS Publication No. (PHS)81-1854, 1981, 71 pp.

NEWMAN, G. Early diagnosis of cancer of the cervix——the detection of high-
risk patients. Geburtshilfe und Frauenheilkunde 32(7): 564-568, July 1972.

NOVAK, J., HYBASEK, I, PELLANT, A. Cancer of the larynx. An
epidemiological study of patients treated during the years 1946-1975 at the
Oral Clinic in Hradec Kralove. Cesk Otolaryngol 26(3): 129-136, 1977.

OCHSNER, A., DEBAKEY, M. Primary pulmonary malignancy. Treatment
by total pneumonectomy. Analysis of 79 collected cases and presentation of
7 personal cases. Surgery, Gynecology and Obstetrics 68: 435-451, 1939.

OLEARCHYK, AS. Gastric carcinoma: A critical review of 243 cases.
American Journal of Gastroenterology 70(1): 25-45, J uly 1978,

ORMOS, J., KARACSONYI, G., BILICZKI, F., SZONYI, F. Lung cancer in the
Hungarian plain. Neoplasma 16(6): 667-675, 1969.

PAPANICOLAOU, G.N., KOPROWSKA, I. Carcinoma-in-situ of the right
lower bronchus: A case report. Cancer 4(1): 141-146, January 1951. .

PEACOCK, E.E., Jr., GREENBERG, B.G., BRAWLEY, B.W. The effect of
snuff and tobacco on the production of oral carcinoma: An experimental and
epidemiological study. Annals of Surgery 151: 542-550, 1960.

PELL, S., D’ALONZO, C.A. A five-year mortality study of alcoholics. Journal
of Occupational Medicine 15(2): 120-125, February 1973.

PERNU, J. An epidemiological study on cancer of the digestive organs and
respiratory system. A study based on 7,078 cases. Annales Medicinae
Internae Fenniae 49(Supplement 33): 1-117, 1960.

PETO, R., SCHNEIDERMAN, M. Quantification of Occupational Cancer.
Banbury Report No. 9, Cold Spring Harbor, New York, Cold Spring Harbor
Laboratory, 1981, 756 pp.

PHILLIPS, R.L., KUZMA, J.W., LOTZ, T.M. Cancer mortality among
comparable members versus nonmembers of the Seventh-Day Adventist
Church. In: Cairns, J., Lyon, J.L., Skolnick, M. (Editors). Cancer Incidence in
Defined Popuaitions. Banbury Report No. 4, Cold Spring Harbor, New York,
Cold Spring Habor Laboratory, 1980, pp. 93-108.

PIKE, M.C., JING, J.S., RASHRIO, LP., HENDERSON, B.E., MENCK, H.R.
Occupation: “Explanation” of an apparent air pollution related localized
excess of lung cancer in Los Angeles County. In: Whittemore, A.S., Breslow,
N.E. (Editors). Energy and Health. Philadelphia Society for Industrial and
Applied Mathematics, 1979, pp. 3-15.

POTTER, E.A., TULLY, MR. The statistical approach to the cancer problem
in Massachusetts. American Journal of Public Health and the Nation’s
Health 35(5): 485-490, May 1945.

POUND, A.W., LAWSON, T.A., HORN, L. Increased carcinogenic action of
dimethylnitrosamine after prior administration of carbon tetrachloride.
British Journal of Cancer 27(6): 451-459, June 1973.

RANDIG, K. Untersuchungen zur Atiologie des Bronchialkarzinoms. [Investi-
gations on the etiology of bronchial carcinoma.] Offentliche Gesundeheits-
dienst 16(9): 305-313, December 1954.
(216)

(217)

(218)

(219)

(220)

(221)

(222)

(223)

(224)

(225)

(226)

(227)

(228)

(229)

(230)

REIF, A.E. Public information on smoking: An urgent responsibility for
cancer research workers. Aspects of Cancer Research 1971-1978: Editorials
from the Journal of the National Cancer Institute. National Cancer Institute
Monograph No. 52. U.S. Department of Health, Education, and Welfare,
Public Health Service, National Institutes of Health, National Cancer
Institute, DHEW Publication No. (NIH)79-1863, September 1979, pp. 123-
128.

REINGOLD, I.M., OTTOMAN, R.E., KONWALER, B.E. Bronchogenic carci-
noma: A study of 60 necropsies. American Journal of Clinical Pathology 20:
515-525, 1950.

RICE, D.P., HODGSON, T.A. Social and Economic Implications of Cancer in
the United States. U.S. Department of Health, Education, and Welfare,
Public Health Service, National Center for Health Statistics, 1978, 82 pp.

RIMINGTON, J. The effect of filters on the incidence of lung cancer in
cigarette smokers. Environmental Research 24(1): 162-166, February 1981.

ROBBINS, W.T. Bronchial epithelium in cigarette-smoking college students.
Journal of the American College Health Association 20(3): 209-211, Febru-
ary 1972.

ROE, F.J.C., CLACK, J.C., BISHOP, D., PETO, R. Comparative carcinogenici-
ty for mouse-skin of smoke condensates prepared from cigarettes made from
the same tobacco cured by two processes. British Journal of Cancer 24(1):
107-121, March 1970.

ROGOT, E. Smoking and General Mortality Among U.S. Veterans, 1954-1969.
US. Department of Health, Education, and Welfare, Public Health Service,
National Institutes of Health, National Heart and Lung Institute, Epide-
miology Branch, DHEW Publication No. (NIH)74-544, 1974, 65 pp.

ROGOT, E. Smoking and mortality among U‘S. veterans. Journal of Chronic
Diseases 27: 189-203, 1974.

ROGOT, E., MURRAY, J.L. Smoking and causes of death among USS.
veterans: 16 years of observation. Public Health Reports 95(3): 213-222,
May-June 1980.

ROSENOW, E.C., CARR, D.T. Bronchogenic carcinoma. CA—A Cancer
Journal for Clinicians 29(4): 233-245, July-August 1979.

ROTHMAN, K.J. Alcohol. In: Fraumeni, J.F., Jr. (Editor). Persons at High
Risk of Cancer. An Approach to Cancer Etiology and Control. New York,
Academic Press, 1975, pp. 139-150.

ROTHMAN, K.J., KELLER, A. The effect of joint exposure to alcohol and
tobacco on risk of cancer of the mouth and pharynx. Journal of Chronic
Diseases 25: 711-716, 1972.

RYAN, R.F., McDONALD, J.R., DEVINE, K.D. The pathologic effects of
smoking on the larynx. Archives of Pathology 60(5): 472-480, November
1955.

SACCOMANNO, G. Radiation exposure of uranium miners. Hearings Before
the Subcommittee on Research, Development, and Radiation of the Joint
Committee on Atomic Energy: Radiation Standards for Uranium Mining.
Congress of the United States, 91st Congress, Ist Session, March 17 and 18,
1969, pp. 301-315.

SADOWSKY, D.A., GILLIAM, A.G., CORNFIELD, J. The statistical associa-
tion between smoking ‘and carcinoma of the lung. Journal of the National
Cancer Institute 13(5): 1237-1258, April 1953.

163
(231)

(232)

(233)

(234)

(235)

(236)

(237)

(238)

(239)

(240)

(241)

(242)

(243)

(244)

(245)

(246)

(247)

164

SAFFIOTTI, U. Experimental respiratory tract carcinogenesis and its rela-
tion to inhalation exposures. In: Hanna, M.G., Jr., Nettesheim, P., Gilbert,
J.R. (Editors). Inhalation Carcinogenesis. Proceedings of a Biology Division,
Oak Ridge National Laboratory Conference, Gatlinburg, Tennessee, October
8-11. 1969. Atomic Energy Commission, Division of Technical Information
EDC Symposium Series No. 18, April 1970, pp. 27-54,

SAFFIOTTI, U., CEFIS, F., KOLB, L.H. A method for the experimental
induction of bronchogenic carcinoma. Cancer Research 28(1): 104-124,
January 1968.

SANDERUD, K. Squamous metaplasia of the respiratory tract epithelium: An
autopsy study of 214 cases. II. Relation to tobacco smoking, occupation and
residence. Acta Pathologica et Microbiologica Scandinavica 43: 47-61, 1968.

SANGHVI, L.D., RAO, K.C.M., KHANOLKAR, V.R. Smoking and chewing of
tobacco in relation to cancer of the upper alimentary tract. British Medical
Journal 1: 1111-1114, 1955.

SATTERLEE, H.S. The problem of arsenic in American cigarette tobacco.
New England Journal of Medicine 254(25): 1149-1156, 1956.

SCHAER, M., MUGGLER, J. Etiological differences between stomach cancer
and cancer of the colon. Sozial- und Praventivmedizin 194): 245-250, July-
August 1974,

SCHAIRER, E., SCHOENIGER, E. Lungenkrebs und Tabakverbrauch. [Lung
cancer and tobacco use.) Zeitschrift fir Krebsforschung 54: 261-269, 1943.

SCHMAUZ, R., COLE, P. Epidemiology of cancer of the renal pelvis and
ureter. Journal of the National Cancer Institute 52(5): 1431-1434, May 1974.

SCHMIDT, W., De LINT, J. Causes of death of alcoholics. Quarterly Journal of
Studies on Alcohol 33(1): 171-185, March 1972.

SCHNEIDERMAN, M.A. Time trends: United States 1953-1973. Laryngo-
scope 88(1, Supplement 8): 6, 44-49, 1978.

SCHOENBERG, B.S., BAILAR, J.C. III, FRAUMENI, J.F., Jr. Certain
mortality patterns of esophageal cancer in the United States, 1930-1967.
Journal of the National Cancer Institute 46(1): 63-73, January 1971.

SCHOTTENFELD, D. Alcohol as a co-factor in the etiology of cancer. Cancer
43(5,Supplement): 1962-1966, May 1979.

SCHOTTENFELD, D., GANTT, R.C., WYNDER, E.L. The role of alcohol and
tobacco in multiple primary cancers of the upper digestive system, larynx,
and lung: A prospective study. Preventive Medicine 3(2): 277-293, June 1974.

SCHREK, R., BAKER, .A., BALLARD, G.P., DOLGOFF, S. Tobacco smoking
as an etiologic factor in disease. I. Cancer. Cancer Research 10: 49-58, 1950.

SCHWARTZ, D., DENOIX, P.-F. L’enquette francaise sur Petiologie du cancer
broncho-pulmonaire. Role du tabac. [French investigation on the etiology of
bronchopulmonary cancer. Role of tobacco.] Semaine des Hopitaux de Paris
33(62/7): 3630-3645, October 30, 1957.

SCHWARTZ, D., DENOIX, P-F., ANGUERA, G. Recherche des localisations
du cancer associees aux facteurs tabac et alcool chez Vhomme. [Research on
the localizations of cancer associated with tobacco and alcoholic factors in
man.] Bulletin de l’Association Francaise pour l’Etude du Cancer 44: 336—
361, 1957.

SCHWARTZ, D., FLAMANT, R., LELLOUCH, J., DENOIX, P.-F. Results of a
French survey on the role of tobacco, particularly inhalation, in different
cancer sites. Journal of the National Cancer Institute 26(5): 1085-1108, May
1961.
(248)

(249)

(250)

(251)

(252)

(253)

(254)

(255)

(256)

(257)

(258)

(259)

(260)

(261)

(262)

(263)

(264)

SEGI, M., FUKUSHIMA, I., FUJISAKU, S., KURIHARA, M., SAITO, S.,
ASANO, K., KAMOI, M. An epidemiclogical study on cancer in Japan. The
report of the Committee for Epidemiological Study on Cancer, sponsored by
the Ministry of Welfare and Public Health. Gann 48(Supplement): April
1957, 63 pp.

SELIKOFF, I.J., BADER, R.A., BADER, M.E., CHURG, J.. HAMMOND, E.C.
Asbestosis and neoplasia. American Journal of Medicine 42(4): 487-496,
April 1967.

SELIKOFF, L.J., HAMMOND, E.C., CHURG, J. Asbestos exposure, smoking,
and neoplasia. Journal of the American Medical Association 204(2): 104-110,
April 8, 1968.

SIMON, D., YEN, S., COLE, P. Coffee drinking and cancer of the lower
urinary tract. Journal of the National Cancer Institute 54(3): 587-591,
March 1975.

STASZEWSKI, J. Palenie a rak wargi, jamy ustnej, migdalkow i krtani.
[Tobacco smoking and its relation to cancer of the mouth, tonsils and
larynx.}] Nowotwory 10(2): 121-132, 1960.

STASZEWSKI, J. Smoking and cancer of the urinary bladder in males in
Poland. British Journal of Cancer 20(1): 32-35, March 1966.

STELL, P.M. Smoking and laryngeal cancer. Lancet 1(7751): 617-618, March
18, 1972.

STELLMAN, J.M., STELLMAN, S.D. What Proportion of Cancers is Attribut-
able to Occupation? Statistical and Social Considerations. Paper presented
at the American Society for Prevention Oncology, Chicago, March 6-7, 1980.

STELLMAN, 8.D., AUSTIN, H., WYNDER, E.L. Cervix cancer and cigarette
smoking: A case-control study. American Journal of Epidemiology 111(4):
383-388, April 1980.

STEVENS, M.H. Synergistic effect of alcohol on epidermoid carcinogenesis in
the larynx. Otolaryngology and Head and Neck Surgery 87(6): 751-756,
November-December 1979.

STEVENS, R.G., MOOLGAVKOV, S.H. Estimation of relative risk from vital
data: Smoking and cancers of the lung and bladder. Journal of the National
Cancer Institute 63(6): 1351-1357, December 1979.

STOCKS, P. Cancer incidence in North Wales and Liverpool region in relation
to habits and environment. British Empire Cancer Campaign Annual Report
35(Supplement to Part II): 66-95, 1957.

SUSSER, M.W. Casual Thinking in the Health Sciences. Concepts and
Strategies of Epidemiology. New York, Oxford University Press, 1973.

SVOBODA, V. An analysis of some possible epidemiological factors involved
in carcinoma of the larynx. Neoplasma 15(6): 677-684, 1968.

TAIRA, N., NAKAYAMA, K., HASHIMOTO, K. Nicotinic acetylcholine
receptors subserving nociception in the dog hindlimb. Japanese Journal of
Physiology 20(5): 571-583, October 15, 1970.

TAKANO, K., OSOGOSHI, K., KAMIMURA, N., KANDA, K., KANE, K.,
KAMIYAMA, R., SAKAMOTO, K., SATO, H., SHIRAI, Y., SEI, M.,
TANABE, T., HORINO, M., MINAMI, Y.L., MOTOJI, H.L., MORITA, R.,
ORIHATA, H.L., HIRAYAMA, T. Schokudogan no ekigaku, toku ni atsui
inshokubutsu, inshu, kitsuen narabi, ni eiyo ketsubo ni tsuit [Epidemiology
of esophageal cancer-with special reference to the significance of hot food
and beverage drinking, smoking, and nutritional deficiency.) International
Journal of Cancer 5: 152-156, 1970.

THOMAS, D.B. An epidemiologic study of carcinoma in situ and squamous
dysplasia of the uterine cervix. American Journal of Epidemiology 98(1): 10-
28, July 1973.

165
(265)

(266)
(267)

(268)

(269)

(270)

(271)

(272)

(273)

(274)

(275)

(276)

(277)

166

TOKUHATA, G.K. Cancer of the Lung: Host and Environmental Interaction.
Pennsylvania Department of Health, Harrisburg, Pennsylvania, September
1972, 48 pp.

TYLECOTE, F.E. Cancer of the lung. Lancet 2(4): 256-257, July 30, 1927.

TYRRELL, A.B., MACAIRT, J.G., McCAUGHEY, W.T-E. Occupational and
non-occupational factors associated with vesical neoplasm in Ireland.
Journal of the Irish Medical Association 64(410): 213-217, April 22, 1971.

UMIKER, W., STOREY, C. Bronchogenic carcinoma-in-situ. Report of a case
with positive biopsy, cytological examination, and lobectomy. Cancer 5(2):
369-374, March 1952.

U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE. Smoking
and Health: A Report of the Surgeon General. U.S. Department of Health,
Education, and Welfare, Public Health Service, Office of the Assistant
Secretary for Health, Office on Smoking and Health, DHEW Publication No.
(PHS)79-50066, 1979, 1136 pp.

U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE. The
Health Consequences of Smoking for Women: A Report of the Surgeon
General. U.S. Department of Health, Education, and Welfare, Public Health
Service, Office of the Assistant Secretary for Health, Office on Smoking and
Health, 1980, 359 pp.

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES. Fourth
Special Report to the U.S. Congress on Alcohol and Health. DeLuca, J.R.
(Editor). U.S. Department of Health and Human Services, Public Health
Service, Alcohol, Drug Abuse, and Mental Health Administration, National
Institute on Alcohol Abuse and Alcoholism, DHHS Publication No.
(ADM)81-1080, January 1981, 206 pp.

US. PUBLIC HEALTH SERVICE. Smoking and Health. Report of the
Advisory Committee to the Surgeon General of the Public Health Service.
U.S. Department of Health, Education, and Welfare, Public Health Service,
Center for Disease Control, PHS Publication No. 1103, 1964, 387 pp.

U.S. PUBLIC HEALTH SERVICE. The Health Consequences of Smoking. A
Public Health Service Review: 1967. U.S. Department of Health, Education,
and Welfare, Public Health Service, Health Services and Mental Health
Administration, DHEW Publication No. 1696, Revised, January 1968, 227
pp.

U.S. PUBLIC HEALTH SERVICE. The Health Consequences of Smoking,
1968. Supplement to the 1967 Public Health Service Review. US. Depart-
ment of Health, Education, and Welfare, Public Health Service, Health
Services and Mental Health Administration, DHEW Publication No. 1696,
1968, 177 pp.

U.S. PUBLIC HEALTH SERVICE. The Health Consequences of Smoking,
1969, Supplement to the 1967 Public Health Service Review. US, Depart-
ment of Health, Education, and Welfare, Public Health Service, Health
Services and Mental Health Administration, DHEW Publication No. 1969—
2, 1969, 98 pp.

U.S. PUBLIC HEALTH SERVICE. The Health Consequences of Smoking. A
Report of the Surgeon General: 1971. U.S. Department of Health, Education,
and Welfare, Public Health Service, Health Services and Mental Health
Administration, DHEW Publication No. (HSM)71-7513, 1971, 458 pp.

U.S. PUBLIC HEALTH SERVICE. The Health Consequences of Smoking. A
Report of the Surgeon General: 1972. U.S. Department of Health, Education,
and Welfare, Public Health Service, Health Services and Mental Health
Administration, DHEW Publication No. (HSM)72-7516, 1972, 158 pp.
(278)

(279)

(280)

(281)

(282)

(283)

(284)

(285)

(286)

(287)

(288)

(289)
(290)
(291)
(292)

(293)

(294)

U.S. PUBLIC HEALTH SERVICE. The Health Consequences of Smoking. A
Report of the Surgeon General: 1973. U.S. Department of Health, Education,
and Welfare, Public Health Service, Health Services and Mental Health
Administration, DHEW Publication No. (HSM)73-8704, 1973, 249 pp.

U.S. PUBLIC HEALTH SERVICE. The Health Consequences of Smoking. A
Report of the Surgeon General: 1974. U.S. Department of Health, Education,
and Welfare, Public Health Service, Health Services and Mental Health
Administration, DHEW Publication No. (CDC)74-8704, 1974, 124 pp.

U.S. PUBLIC HEALTH SERVICE. The Health Consequences of Smoking. A
Report of the Surgeon General: 1975. U.S. Department of Health, Education,
and Welfare, Public Health Service, Health Services and Mental Health
Administration, DHEW Publication No. (CDC)76-8704, 1975, 235 pp.

U.S. PUBLIC HEALTH SERVICE. The Health Consequences of Smoking. A
Reference Edition. U.S. Department of Health, Education, and Welfare,
Public Health Service, Center for Disease Control, DHEW Publication No.
(CDC)78-8357, 1976, 657 pp.

VALKO, P. Koureni a vyskyt zhoubnych novotvaru hrtanu. [Smoking and
occurrence of malignant tumors of the larynx.] Ceskoslovenska Otolaryngolo-
gie 1: 102-105, 1952.

VINCENT, R.G., MARCHETTA, F. The relationship of the use of tobacco and
alcohol to cancer of the oral cavity, pharynx or larynx. American Journal of
Surgery 106(3): 501-505, September 1963.

VINCENT, R.G., PICKREN, J.W., LANE, W.L., BROSS, I, TAKITA, H.,
HOUTEN, L., GUTIERREZ, A.C., RZEPKA, T. The changing histopathology ©
of lung cancer. A Review of 1682 cases. Cancer 3% 4): 1647-1655, April 1977.

WAGONER, J.K., ARCHER, V.E., CARROLL, B.E., HOLADAY, D.A., LAW-
RENCE, P.A. Cancer mortality patterns among U.S. uranium miners and
millers, 1950 through 1962. Journal of the National Cancer Institute 32(4):
787-801, April 1964.

WAGONER, J.K., ARCHER, V.E., LUNDIN, F-E., Jr.. HOLADAY, D.A.,
LLOYD, J.W. Radiation as the cause of lung cancer among uranium miners.
New England Journal of Medicine 273(4): 181-188, July 22, 1965.

WAGONER, J.K., MILLER, R.W., LUNDIN, F-E., Jr.,. FRAUMENI, J.F., Jr.,
HAIJ, M.E. Unusual cancer mortality among a group of underground metal
miners. New England Journal of Medicine 26%6): 284-289. August 8, 1963.

WASSINK, W.F. Ontstaansvoorwaarden voor longkanker. [Conditions for the
origin of lung cancer.] Nederlands Tijdschrift voor Geneeskunde 92(46):
3732-3747, November 13, 1948.

WATSON, W.L., CONTE, A.J. Smoking and lung cancer. Cancer 7(2): 245-249,
March 1954.

WEIR, J.M., DUNN, J.E., Jr. Smoking and mortality: A prospective study.
Cancer 25(1): 105-112, January 1970.

WEISS, W. Lung cancer mortality and urban air pollution. American Journal
of Public Health 68(8): 773-775, August 1978.

WEISS, W. The cigarette factor in lung cancer due to chloromethyl ethers.
Journal of Occupational Medicine 22(8): 527-529, August 1980.

WEISS, W., BOUCOT, K.R., SEIDMAN, H., CARNAHAN, W.J. Risk of lung
cancer according to histologic type and cigarette dosage. Journal of the
American Medical Association 222(7): 799-801, November 13, 1972.

WEST, D.W. An assessment of cancer risk factors in Latter-day Saints and
non-Latter-day Saints in Utah. In: Cairns, J., Lyon, J.L., Skolnick, M.
(Editors). Cancer Incidence in Defined Populations. Banbury Report No. 4,
Cold Spring Harbor, New York, Cold Spring Harbor Laboratory, 1980, pp.
31-49.

167
(295)

(296)

(297)

(298)

(299)

(300)

(301)

(302)

(303)

(304)

(305)

(306)

(307)

(308)

(309)

(310)

(311)

(312)

(313)

168

WICKEN, A.J. Environmental and Personal Factors in Lung Cancer and
Bronchitis Mortality in Northern Ireland, 1960-1962. London, Tobacco
Research Council, Research Paper No. 9, 1966, 84 pp.

WIGLE, D.T., MAO, Y., GRACE, M. Relative importance of smoking as a risk
factor for selected cancers. Canadian Journal of Public Health 71(4): 269-
275, July-August 1980.

WIGLE, D.T., MAO, Y., GRACE, M. Smoking and cancer of the uterine cervix:
Hypothesis. (Letter). American Journal of Epidemiology 111(1): 125-127,
1980.

WILLIAMS, M.J. Extensive carcinoma-in-situ in the bronchial mucosa
associated with two invasive bronchogenic carcinomas. Report of case.
Cancer 5{4): 740-747, July 1952.

WILLIAMS, R.R., HORM, J.W. Association of cancer sites with tobacco and
alcohol consumption and socioeconomic status of patients: Interview study
from the Third National Cancer Survey. Journal of the National Cancer
Institute 58(3): 525-547, March 1977.

WINKELSTEIN, W., Jr. Reviews and commentary. Smoking and cancer of
the uterine cervix. Hypothesis. American Journal of Epidemiology 106(4):
257-259, October 1977.

WINN, D.M., BLOT, W.J., SHY, C.M., PICKLE, L.W., TOLEDO, A., FRAU-
MENI, J.R., Jr. Snuff dipping and oral cancer among women in the southern
United States. New England Journal of Medicine 304(13): 745-749, March
26, 1981.

WOLFF, G., LAUTER, J. Zur Epidemiologie des Magenkrebses. I. Mitteilung.
{On epidemiology of gastric cancer. First Communication.] Archiv fur
Geschwulstforschung 46(1): 1-14, 1976.

WORLD HEALTH ORGANIZATION. World Health Statistics Annual. Vital
Statistics and Causes of Death. Geneva, World Health Organization, 1977.

WORLD HEALTH ORGANIZATION. World Health Statistics Annual. Vital
Statistics and Causes of Death. Geneva, World Health Organization, 1980.

WRIGHT, N.H., VESSEY, M.P., KENWARD, B., McPHERSON, K., DOLL, R.
Neoplasia and dysplasia of the cervix uteri and contraception: A possible
protective effect of the diaphragm. British Journal of Cancer 38(2): 273-279,
August 1978.

WYNDER, E.L. The epidemiology of cancers of the upper alimentary and
upper respiratory tracts. Laryngoscope 8&1, Supplement 8, Part 2): 50-51,
January 1978.

WYNDER, E.L., BROSS, IJ. A study of etiological factors in cancer of the
esophagus. Cancer 14(2): 389-413, March/April 1961.

WYNDER, E.L., BROSS, LJ., CORNFIELD, J., O'DONNELL, W.E. Lung
cancer in women. A study of environmental factors. New England Journal
of Medicine 255(24): 1111-1 121, December 13, 1956.

WYNDER, E.L., BROSS, LJ., DAY, EL A study of environmental factors in
cancer of the larynx. Cancer 9(1): 86-110, January-February 1956.

WYNDER, E.L., BROSS, LJ., FELDMAN, R.M. A study of the etiological
factors in cancer of the mouth. Cancer 10(6): 1300-1323, November-Decem-
ber 1957.

WYNDER, E.L., CORNFIELD, J. Cancer of the lung in physicians. New
England Journal of Medicine 248(11): 441-444, March 12, 1953.

WYNDER, E.L., COVEY, LS., MABUCHI, K., MUSHINSKI, M. Environmen-
tal factors in cancer of the larynx. A second look. Cancer 38(4): 1591-1601,
October 1976.

WYNDER, E.L., GOLDSMITH, R. The epidemiology of bladder cancer. A
second look. Cancer 40(3): 1246-1268, September 1977.
(314)

(315)

(316)

(317)

(318)

(319)

(320)

(321)

(322)

(323)

(324)

(325)

(326)

(327)

(328)

(329)

(330)

WYNDER, E.L., GORI, G.B. Contribution of the environment to cancer
incidence: An epidemiological exercise. Journal of the National Cancer
Institute 58(4): 825-832, April 1977.

WYNDER, E.L., GRAHAM, E.A. Tobacco smoking as a possible etiologic
factor in bronchiogenic carcinoma. A study of six hundred and eighty-four
proved cases. Journal of the American Medical Association 143(4): 329-336,
May 27, 1950.

WYNDER, E.L., HOFFMANN, D. Tobacco and tobacco smoke. Seminars in
Oncology 3(1): 5-15, March 1976.

WYNDER, E.L., HULTBERG, S., JACOBSSON, F., BROSS, I.J. Environmen-
tal factors in cancer of the upper alimentary tract. A Swedish study with
special reference to Plummer-Vinson (Paterson-Kelly) syndrome. Cancer
10(3): 470-487, May/June 1957.

WYNDER, E.L., KMET, J., DUNGAL, N., SEGI, M. An epidemiological
investigation of gastric cancer. Cancer 16(11): 1461-1496, November 1963.

WYNDER, E.L., MABUCHI, K., BEATTIE, E.J., Jr. The epidemiology of lung
cancer. Recent trends. Journal of the American Medical Association 213(13):
2221-2228, September 28, 1970.

WYNDER, E.L., MABUCHI, K., MARUCHI, N., FORTNER, J.G. A case
control study of cancer of the pancreas. Cancer 31(3): 641-648, March 1973.

WYNDER, E.L., MABUCHI, K., MARUCHI, N., FORTNER, J.G. Epidemiolo-
gy of cancer of the pancreas. Journal of the National Cancer Institute 50(3):
645-667, March 1973.

WYNDER, E.L., MABUCHI, K., WHITMORE, W-F., Jr. Epidemiology of
adenocarcinoma of the kidney. Journal of the National Cancer Institute
536): 1619-1634, December 1974.

WYNDER, E.L., MUSHINSKI, M.H., SPIVAK, J.C. Tobacco and alcohol
consumption in relation to the development of multiple primary cancers.
Cancer 40(4): 1872-1878, October 1977.

WYNDER, E.L., NAVARRETE, A., AROSTEGUI, G.E., LLAMBES, J.L.
Study of environmental factors in cancer of the respiratory tract in Cuba.
Journal of the National Cancer Institute 20(4): 665-673, April 1958.

WYNDER, E.L., ONDERDONK, J., MANTEL, N. An epidemiological investi-
gation of cancer of the bladder. Cancer 16(11): 1388-1407, November 1963.

WYNDER, E.L., STELLMAN, S.D. Comparative epidemiology of tobacco-
related cancers. Cancer Research 37(12): 4608-4622, December 1977.

WYNDER, E.L., STELLMAN, S.D. Impact of long-term filter cigarette usage
on lung and larynx cancer risk. A case-control study. Journal of National
Cancer Institute 62(3): 471-477, March 1979.

WYNDER, E.L., WRIGHT, G. A study of tobacco carcinogenesis. 1. The
primary fractions. Cancer 10(2): 255-271, March/April 1957.

YESNER, R. Histologic typing of lung cancer with clinical implications.
Frontiers of Radiation Therapy and Oncology 9: 140-150, 1974.

YOSHIDA, O., MIYAKAWA, M., HARADA, T., OKADA, K. Bokogan no
ekigaku ni okeru mondaiten. [Problem points in epidemiology of bladder
cancer.] Nihon Rinsho 26(8): 1850-1854, August 1968.

169
PART Ill. MECHANISMS OF
CARCINOGENESIS

171

377~310 0 - 82 - 13
METHODOLOGY OF EXPERIMENTAL
CHEMICAL CARCINOGENESIS

Experimental Assessment of Carcinogenicity

In order to determine the possible carcinogenicity of tobacco
smoke constituents, the same procedures should be employed as are
used for other substances. Various criteria and guidelines for
carcinogenicity tests have been advocated by several governmental
and international agencies and by various advisory groups. For
example, the World Health Organization (WHO) (29), the Interna-
tional Agency for Research on Cancer (IARC) (8), the Environmental
Protection Agency (3), the Food and Drug Administration (4), the
National Cancer Institute — National Toxicology Program (22),
Health and Welfare of Canada (2), and the Health Council of the
Netherlands (13), as well as others, have issued guidelines for the
testing of compounds for different aspects of acute and chronic
toxicity.

Chemicals

As a first step in the testing of any material for possible
carcinogenicity, the researcher should obtain a complete physico-
chemical characterization of the material. Examinations by such
techniques as thin-layer, gas-liquid, or high performance liquid
chromotography should afford some idea of whether the materia! is
homogeneous or a mixture of components. If the last is the case,
identification of the individual components and determination of the
level of each in the mixture are highly desirable. Otherwise, the
validity and significance of the results may be questioned.

Factors Influencing Carcinogenicity

In tests for possible carcinogenicity, several factors influence the
outcome of any study. Those relevant to the compound are the route
of administration and the dose and frequency of administration.
Factors relating to the animal are the species, strain, sex, age, diet,
spontaneous tumor incidence, and immunological status.

Route of Administration
Oral administration

In addition to being a logical technique for testing compounds that
may be ingested by humans, oral administration is also useful for
compounds that may be inhaled as dusts, cleared from the airways
by ciliary action, and then swallowed. Compounds may be mixed in
the feed, given as aqueous solutions instead of normal drinking
water, given by gavage at appropriate intervals, or even given in
capsules. If the compound is mixed with the feed, the uniformity of

173
mixing, the stability in the diet, and the nonreactivity with the feed
are factors of concern. Volatile compounds should not be given in the
diet, for the resultant loss will lead to inaccuracies in dose levels. If
given in the drinking water, solubility and stability must be
considered.

Dermal

The dermal route simulates exposure of the skin as it occurs in
occupational situations or in the use of cosmetics, and has been used
as a standardized carcinogenicity assay. Application of a solution of
the test-material by means of a pipet should be made in an area that
cannot be reached by the animal. Otherwise, the animal will lick the
treated area so that oral ingestion occurs. To avoid the animals’
licking each other, single caging is desirable. In this type of test,
mice, hamsters, rabbits, and sometimes rats are used. For cutaneous
application, mice of the BALB/c, C3Hf, or DBA strains or the non-
inbred Swiss strain are most responsive. SENCAR mice have been
especially bred for sensitivity in initiation-promotion assays. The
skin should be clipped before application of the test compound, but
abrasion or mechanical injury of the skin should be avoided.

Implantation: Subcutaneous and Intramuscular

Although subcutaneous injection of polycyclic aromatic hydrocar-
bons in mice has proved to be quite reliable as a test system, the use
of this test in other species has led to controversial results. The
induction of tumors at the implantation site, especially in rats, by
inert materials of the proper size, by saline solutions, or by oily
solvents has indicated the limitation of this test.

Injection: Intraperitoneal and Intravenous

Intraperitoneal and intravenous injections may be used to test
drugs, but for various reasons are not suitable for repeated dosing.
They are useful for administering a single dose or a few doses of
potent carcinogens for model experiments. With this technique,
exposure of personnel to carcinogens, is minimized.

Inhalation

Inhalation is the major route by which persons are exposed to
cigarette smoke. For laboratory study, complex installations, such as
pumps or metering devices, are needed to allow uniform delivery of
the test material to the experimental animals. Scrubbers and other
devices are required to prevent exposure of any personnel working in
the area. A test by the inhalation route usually costs much more
than studies using other routes of administration.

174
In lieu of using large inhalation chambers in which animals are
exposed, it is possible to use chambers into which the head and nose
of individual animals are fitted. The test material is then forced into
the chamber, resulting in an inhalation exposure. Relatively few
animals can be treated with a given chamber by this method,
however.

Factors that should be considered in evaluating the results of the
test are effects on secretion of mucous, alteration of pulmonary
ventilation, and possible toxicity to the cilia in the respiratory tract.

The dilemma is that in rodents the anatomy and physiology of the
respiratory tract and the biochemistry of the lung differ from that of
humans and that animals anatomically resembling the human most
closely are too expensive and have lifespans too long to permit their
use in routine tests.

For inhalation tests of the carcinogenicity of tobacco smoke and
various fractions of tobacco smoke, hamsters are preferable to rats
and mice because they respond with a higher incidence of airway
tumors (6).

Higher dose levels, greater frequency of administration, and
longer periods of observation are required for weak carcinogens than
are needed for potent ones. For example, potent carcinogens such as
7,12-dimethylbenziaJanthracene or nitrosomethylurea can induce
cancers in certain animals after a single dose. On the other hand, a
single or very low dose of compounds such as N-2-fluorenylacetam-
ide, safrole, and dioxane may not lead to tumors within the lifespan
of the animal.

Animal Factors
Species

The choice of species rests on several factors, including lifespan,
size, sensitivity to a specific class of compound, and availability.
Early studies on skin painting of benzo[a]pyrene showed that mice
and rabbits were responsive, while the few other species tested were
less responsive. Guinea pigs are not suitable for testing aromatic
‘amides and amines or their precursors. They either lack the enzyme
system that activates aromatic amines or degrade the activated
metabolite so rapidly that there is no effect. Overall, mice are the
most useful animals for skin painting bioassays; rats are useful for
test material that might be fed, especially with nitroso compounds or
aromatic amines; and hamsters seem better suited for inhalation
studies on tobacco smoke or its components.

Larger species including the rabbit, dog, and primate require a
longer time to obtain results; they are expensive to purchase, to
maintain, and to test; and they are not always readily available.

175