TSE

TABLE A—Ontline of methods used in retrospective studics of smoking in rel

Authur,
year,
country,
reference

Sex of
cases

Wynder and M
Cornfield,
1953,
U.S.A,
(314),

Koulumies,
1953,
Finland

C4Sty,

M-F

Lickint,
1963,
Germany
(170).

M-F

Breslow
etal,
1064,
U.S.A.
(42),

Watson and

Grell, ” M
1954,
Switzerland
(107),

Number of porsons
Cases

63 physicians reported in AMA
Journal ag dying of cancer of
the lung.

812 lung cancer patients ding-
nosed at one hospital.

246 lung cancer patients in a
number of hospitals and clinics.

618 Jung cancer patients in Mt
California hospitals,

801 patients at Memorial Hospi-
tal with lung cancer.

135 men with diagnosis of bron-
chial carcinoma.

and method of selectiun
Controls

133 physicians of same group dying of can-
cer of certain other sites.

300 mule outpatients of same hospital over
40 years of age.

2,002 sample of persons without cancer liy-
ing in the same area and of the same sex
and age range ay cases.

G1H patients admitted to same hospitals about
the same time, for conditiona other than
enncer or chest digcuge, mutched for race,
sex, und age group,

468 patients of same clinic
period with diagnoses
cancer.

during same
other than lung

185 similar hospital patients with dingnoses
other thun hing cancer, and of the same
BR,

ation to lung cancer (cunt.)

Collection of data

Mail questionnaire to eatates of decedents,

Cases and controla questioned about amuking
habits when taking case histurics, 361 di-
Agnoges confirmed histologically; 494 ding
noses confirmed by clinical,
operative data.

X-ray, and

Personal interviews by ataff members of cu-
operating hospitals and clinics.

Cusea and controls
interviewers,
samc person,

trained
palr by the

questloned by
cach matched

The 769 consecutive patients of case and
control groups were tuestioned by the
same trained interviewer. Control group
includes patienty with oral and esophageal
cancer and bronchitis.

Personal interviows, all by the game persun.
ZSE

TABLE AS Outline of methods used in retrospective studies of smoleing in relation to hou cancer (cunt.)

 

 

 

 

 

 

 

 

Author,

yenr, Sex of Number of persons and methud of selection
country, cnges -—--- Collection of data
reference Cases Controls

Randig, M-F 44R lung enncer patients in a h12 patients with other dingnoses, matched Controls were interviewed at about the same
134, nutnber of West Rerlin hospi- fay aie. time as the cuses, ench case-control palr
Germany tats, by the same physician,

(293),

Wyner etal, F 105 patients with lung cancer in 1,801 patients at Memorial Center with tue Cases: Personal interview or questionnaire
1956, yeveral New York City hospi- mors of sites ather than respiratory or mailed tu cluse relatives or friends.
U.S.A. tals. upper alimentary, Controls: Personal interview.

(str),

Segi ct al, M-F 207 patients with lung cancer in 5,035 patients {vee of cancer in 420 Jocal Cusex and controls by personal Interview
1957, 33 hospitals in all parts of health centers, selected to approximate using long questionnaire on occupational
Japan the country. the sex and axe distributions uf cuses. and medical histury and living habits.
(250),

Mills and M-F 578 residents of defined areas $310 population sample approximately pro- Cases: From death certificates, hospital rece
Porter, dying of respiratory cancer. bortivonal to casea ag rewards ureas of resis ords, and close relatives or fricnads.

157, dence, and 10 years or more in the area, Controls: Persunal home visita or telepbone
U.S.A. calls, usually interviewing housewife.
(487).

Stocks, M-F 2,356 patients suffering from or 2,382 unselected patients of the same area Cases: Histories tuken at the hospital from
1957, dying with lung cancer within admitted fur conditions other than cancer. relatives by health visitors.

England certain orcas, Controls: Personal Interview in hospital.
(264),

Schwartz and M 602 patients with bronchopul- L204 patients (3 groups) in same hospitals Personal interviews in the hospital: cascs
Denoix, monary cancer in hospitals, with other cancer, with nonmalignant ill- and controls at about the same time by
1967, tess, and accident cases, mutched by age
France

(247),

Kroup,

the same interviewer.

 
Taste A3.—Oulline of methods used in retrospective studies of smoking in relation to lung cancer (cont)

 

 

 

 

 

 

 

 

 

 

 

Author,
year, Sex of Number of persons and method ef sclection
country, eoacy Collection of data
reference Cases Controls
Hacnazel and F 168 lung cancer patients avnil- 339 patients in same hospital and service at Personal interviews by resident, medical so.
Shimkin, able for interview in 20 has» xame time, next older and next younger cinl worker, or clinle seerclury.
196K, pitaly, than ench cue.
U.S.A.
(iis),
Lombard and M 600 men dying of lung cancer, 4,238 controls in 7 groups inchiding volun Personal Interviews by trained workers.
Snegireff, microscopleally confirmed. teers, huspital and elinle patients, random
1069, population sample, and hovse-do-house sure
U.S.A, vey samples.
(176).
Pernu, M-F 1,€06 respiratory cancer patients 1,773 concer-free persons recruited by Parish Cases: From case hiytorics or mailed ques-
1960, in 4 hospitals and from cuncer Sisterg of 2 institutey in all parts of the tionnaires.
Finland registry. country, Controls: Questionnnires distributed by Tar
(298). ish Sisters.
Haenszel M 2,191 sample of 10 percent of 31,616 random sample from Current Popu- Cuses: By mail from certifying physicians
etal, white male lung cancer deaths lution Survey, and family informants.
1962, in the U.S.A. in 1988, Controls: Persons) interview by censug wniue
ULS.A. mornlors,
(ile),
Lancaster, M 238 hospital patients with Jung 476 in 2 groups, 1 with other cancer, 1 with Personal interviews of bath eases ond cone
1962, cancer. some uther disease, matched by sex and trols in haypitals,
Australia BEG,
(153).
Hoensze) and F 749 sample of 10 percent of 34,339 random sample from Current Popula- Cases: By mail from certifying physiciang
Toecuber, white female lung cancer deaths tion Survey used to estimate population and family informants.
1964, in the U.S.A. in 1968 and buse. Controls: Personal interview by census enu-
U.S.A. 1969,

merators,
(115),

 

 
“St

TABLE A3.—Oxtline of methods used in retrospective studies of smoking in relation to lung cancer (cont.)

 

Author,
year,
country,
reference

Sex.of Number of persana and method of aclection

 

cascs
Cases Controls

Collection of data

 

Wieken,
1966,
Northern
Ireland
(903),

M-F 964 patients with primary Jung 954 age and sex-matched controls from same
cancer. locale and deceased from nonrespiratory
disenuca,

Interviews with relatives.

 

Gelfand ct ab,
JGR,
Rhodesla
(9¥).

M 32 patlenta with bronchogenic 82 ae ntl nexematehed pattents
cuncur,

Monpltallzatlon titerviews.

 

Hitosugi,
19Gs,
Japan
(126),

M.-F 185 pationty with Jung cancer 491 pertona sex-matched from almilar alr
pollution regions,

Cases? Hospital interviews.
Controls: Interviews by trained public health
nurscs,

 

Brodyhaw and
Schontund,
1969,

South Africa
(Natal)
(47).

M 45 Zulu patients with lung can- S41 Zulu patients without lung cancer,
cer,

Interviewed by trained African social worker,

 

Ormus et al,
1969,
Hungary
(204).

M-F 118 patients with lung cancer, 3,089 control persuns without data on health
history.

Cases: Datu derived from enae histories und
interviews with relatives,

Controls: Interviews with a random saniple
of troin passengers.

 

Wynder, et al,
1970
U.S.A,
(S24).

M-F 240 patients with Kreyberg Type 480 oge and sex-matched patients
I lung concer.

Hospitalization interview,

 
GSE

TaBre Ad.—Group characteristics in retrospective etudies on ling cancer and tobacco use

SM = Smokers.

NS =: Nonsmokers,

 

 

 

 

 

 

 

 

 

 

 

 

 

Males Females
Author, Cases Controls Cases Controls
year, Relative Relative Comments

reference Percent Percent Pereent Percent risk Pereent Percent Percent Pereent — risk

none heavy non- heavy ratio none hea non heavy ratio

Number smokers smokers) Number smokers smokerst SM:NS? Number smokers smokers! Number amokers smokers! SM;NS?
Muller, &G 35 65.1 86 16.3 36.0 75.4 (*) (4) (4) (*) () (4)

1939 (196).

Schairer and 93 3.2 31.2 270 16.9 9.3 26.7 (9 io) 9 (4) (9 (9) ... 1G female
Schoniger, cases nat
1943 (242), analyzed.

Potter and 43 7.0 30.2 2,804 26.0 23.0 U1 (4) (9 (4) Cy) (4) (*)

Tully,
M945 (292),

Wassink, 134 4.8 54,8 100 19.2 19.2 4.7 (4) (4) (*) (1) (*) {4} ve. Percentages
1948 (904), estimated

from chart.

Schrek et al, K2 14.6 18.3 522 23.9 9.2 1.8 (*) (4) (') (4) (4) (4)

L950 (246),

Milla and 444 72 430 30.6 6.7 (4) (4) (4) (*) (4) (4)

Purter,
1950 (46),

Levin et al., 246 16.8 481 21,7 1.6 (4) (*) (4) (4) (*) {') vee Quantity
1050 C477), amouhked not

considered,

Wynder and G05 1.3 $1.2 780 14.6 19,1 13.0 40 57,5 25.0 552 79.6 1.2 2.9
Graham,

1950 (316).

 
gst

TAULE Ad.—Group characteristics tn retrospective studies an Qui

SM = Smokers.

 

NS 2s Nonumokers.

cancer und tobacce use (cortt.)

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Males Femites
Author, Cases Controls : Cases Controls ;
your, ~ Relative Retative Comments
reference Percent Percent Percent Percent visk Percent = Pereent Percent Pereent =o risk
none heavy non- heavy ratio none heavy non- heavy ratio
Number smokers smokers’ Number smokers smokers! SM:NS? Number smukers smokerst Number amokers smokers! SM:NS?
McConnell Ou 3.4 38.5 186 6.5 23.2 1,2 1 ST. 14 78.6 2.8
eval,
1952 (180).
Doll and Hill 1,957 0.5 25.1 1,357 45 13.4 9.4 108 37.0 1 108 54.6 0.9 2.1.00 Porcentige
1962 (79). “heavy”
atmmukers,
vniderstated,
Sadowsky 477 38 G15 2 3.9 (*) {*) (4) (4) (4) (4) Gradient
etal, with amount
1953 (292), smoked.
Wynder and 63 4 C76 133 20.6 29,3 36.1 (*) (4) (*') () (*) (*)
Cornfield,
1953 (srs),
Koulumies 12 0.6 58.9 300 18.0 25.0 36.0 os (4) (*) (4)
1954 (fo).
Lickint 224 1.8 35.8 1,000 16.0 4.8 310-4 22 G40 4.6 1,002 90.4 O1 5.3 ~
1953 (870).
. Breslow el ab, 493 a7 TA 518 10.8 42.7 4.2
A954 (an),
Watson and 265 1 m4 287 01 61.6 5.6 6 oH 28 1H 42.0 bok °
Cunte,
1954 (305),
Gxell, Wo Q,7 Gs.1 Wah 16.0 14.0 _— “GR ~ Cy ~— “| yy ~ Oyo (ty Oo
1054 (107),
LS

TABLE A4.—Group characteristics in retrospective stiudics on lang cancer and tobacco use (cont.)

SM = Smukers,

NS = Nonsmokers.

 

 

   

 

 

 

 

 

 

 

 

 

Males Females
Author, Cases Controls Chacs Controls
yeur, an en te ee ee -— Kelutive--- a ee ee ne ne te ee Relative Comments
reference Bereent | Pereent Perernt Percent risk Pereent Percent Percent Percent — risk
Num. vole henvy none heavy ratio Num- none heavy hone heavy rala
ber smokers oxmokers! Number smokers amokers! SMiNS? ber amokers gyimokers! Number smokers smokers! SM:INS?
Randig, 415 1.2 34,2 381 5.8 17.9 55.1 33 51.6 3.0 131 70.3 0 2.2
1054 (278),
Wynder etal, (4) (*) () (*) (‘) (4) 105 66.2 16.2 1,304 66.0 3.4 14
ASG (att).
Segietal, 166 ' 2,124 ‘ a Quantities
1U67 (250), amohest stated
UY AVE
only, Diterences
are tatoo eally
sidnitiennt,
Mills and 484 ad 26.0 1,588 27.6 5.3 4.2 o4 83.0 4.3 3,722 13.3 0.5 0.6 Percent “heavy'
Porter, amuhers uridine
1957 stated. Only
(187), S0l; survey
VOspoase WMOENS
female coses,
Stocks, 2,101 19 28.2 6,960 8.7 22.3 4.9 255 57.6 17.2 3,402 68.6 10.7 LG
1037 (268).
Schwartz and — 602 1.0 58.2 1,204 2.5 36.2 10.4 (4) (4) () () ) ()
Denoix,
WOT (247),
Hacnszeland (4) (4) (4) () ) ) 15x 51.9 HG 339 69.6 8.2 1 _

Shimkin,
1958 (738),
BSE

TABLE A4.—Group characteristics in retrospective stiulics on lung cancer and tobacco use (cont.)

SM = Smokers. NS = Nonsmokers.

 

 

 

 

 

 

 

 

 

Males Females
Author, Cases Controls Cases Controls .
year, Relative Relative Comments
reference Percent Percent Percent Percent risk Percent Percent Percent Percent risk
Num- none heavy none envy ratio non- heavy none heavy ratio
ber smokers smokers! Number smokers smokers! SM:NS? Number smokers smokers! Number smokers smokers! SM:NS?

Lombard and 500 1.6 ne 4,238 11.0 19 (9 rem) i) () (4) (4) Authurs'
Snegireff, culeulations for
1959 (176). heusy smoking

Daseibun lifetime
number of packs
of cigarettes,

Pernu, 1,477 6.6 34,5 713 37.2 20.8 8.4 129 35.9 c6.4 1,060 91.6 | 0.7 1,9 Quantities
1960 (2f2), wiven only in

Kran per day.

Haenszel 2,191 3.4 41.9 () 16.2 12.0 6.2 (4) (4) (4) (4) @) “4 vee) Population

etal, sample of
1962 (y22)}. 31,510 used ag

Dase. Not a cages
control study.
Lancaster, 238 2.5 86.1 476 20,1 912 9.8 (*‘) (4) (*) (4) (+) (4)
1962 (159).
Haenszeland — (‘) (9 () () () (4) . 749 60.9 IS rc) 67.3 2.5 1.3 Population
Taeuber,

1964 (175).

gample of
Sa, 330 aed
as base. Not
a case-cantral
study,
6SE

Taw yy Ad—-Clroup characteristies in tetraspective stidies on hang eameer wud tohaces se (cont)

 

 

 

 

 

 

 

 

 

 

 

 

SM = Smokers, NS. Nonsmokers,
Males Females
Author, Cases Controls Cases Controls
year, Relative Relative Cunmments
reference Pereent. Pereent Percent Percent risk Pereent Percent Percent Percent — risk
Num. none heavy nuns heavy ratio none heavy none henvy ratia
ber smokers smokers! Number smokers smokers! SM:NS* Number smokers smokers! Number smokers smokers! SM:NS?
Wicken, Od 4.0 40.0 803 14.0 22.0 3.8 151 5x0 29.0 161 80.0 17.0 2.9 Heavy sinokers—
1966 (708). renter Chr
28 on stny.
Gelfand et ul., 32 6.3 see 32 63.0 sae 525.3 (") (4) i) () () (")
W968 (94).
Hlitosugi, 124 5.6 67.8 1,839 13.2 66.0 2.6 61 84.1 6.6 2,362 80,5 2.9 2.30 Air pollution
19GR (225), found to have
no effeel on
Vung vapeu
yates of one
smokers. Peavy
emoherss oreite
trthan la day,
Bradshaw and = 45 0.0 bes 34l 31.7 on bes () (9 (y (y (4) ay -
Schanland,
1969 (41).
Ormos otal, os 15 68.5 1,811 42.9 38.9 9.3 a4 OGM uo 1,278 B17 9.1 0.2 Heavy smokers
1uGd (204), greater thin
15 aday.
Wynderetol, 210 1.4 67.5 420 21.0 40.9 220.8 30 16.7 44.0 132 57.6 23.3 6.78 leavy
V970 (334). : amukers—
greater than
20 w day,
’ For this table, heavy smokers nre defined as those smoking 20 or more 2 Based upon fewer than $ cuse nonsmokers.
Cigaretles per day, unless otherwise stated, Does not apply.

+ Computed according to method of Corntleljl, J. (61).
TABLE A7.—Grouping of pulmonary carcinomas

Group I:
A. Epidermoid carcinoma.
B. Smali cell anaplastic carcinoma (“oat-cell” carcinoma).

Group II:
A. Adenocarcinoma.
B. Bronchiolo-alveolar cell carcinoma.

€. Carcinoid tumor.
D. Mucous gland tumor.

Extra (not included in I and If):
A. Large cell undifferentiated carcinoma.
B. Combined epidermoid and adenocarcinoma.

Unsuitable for diagnosis.

Source: Kreyberg, L. (1535).

360
T9E

Author,
your,
country,
reference
Little et al,
1964,
ULS.A. (173).

TABLE

Number

CASCS

NS woe eee eee eee B
SM ceereeeeveeae 12

NS = Nonamukers. SM = Smokeru.

Results

Po! levels in various tiesuce (pe/g tissue)

Peribronchia! Bronchial
lymph nodes Lung (average) epithelium
0.011 0.001-2 negligible
0.011 0.008 0,028-1,25

Al2.—Autopsy studica concerning the presence of radiouctivity in the lungs of smokers

Comments

Vertebral bodics, renal
cortex, spleen, and
urinary bladder showed
no differences,

 

Hill, 1965,
ULS.A. (129),

NS vicceceeeereeee 6
EC) a |

Mean Pot! levela in various tissucs (pe/kg tiaaue)

Bronchial tree Alveolac Total lung Liver Kidney
al 3.4 3.2 14.8 18.0
13 9.9 8.6 20,0 20.6

The authors found no
excessive concentrations
at bronchial bifurca
tions.

 

Little et al.,
1965,
U.S.A. (174),

 

Po?!l® levela in various epithelial tiasuc regions of lung (pe/g)t
Site:
Mainstem bronchus ooo... cc cece eee e ee eee rr eee neste
Lobar bronchus wi. see ese aee
Basal segmental bronchus
Upper segmentul bifurcation
Lower segmental bifurcation

   
 

The autharg noted con.
aiderable  interpersunal
variation but did lind a
trend relationship be»
tween increnusel daily
consumption and ine
ereased Bot!" Jevely in
hung parenchynia, No
guch relationship waa
noted for uge of indi-
vidual ut death or for
fotal puck-yeurs,

+Smokery only.
Z9L

TABLE A12.—Autopsy studies concerning the presence of radioactivity in the lungs of smokera (cont,)

NS = Nonsmokers. SM == Smokers.

 

 

 

Author,
year, Number
country, of Results Comments
reference cases
Ferriand Mean Pot! levels in various tisaues (pe/g wet tieeve)
Baratta, Lung Liver Kidney
1966, NS cicceseeees ee sll 0.031 0.103 0.080
U.S.A. (95). SM vec scsseacene ed 0,066 0.125 0.070
Rajewsky and Moan Pot! levela tn various tiaauer (pe/7) ¢Data not given. Smokers
Stablhofen, Lung parenchyma Bronchial tree Bronchial btfureation were considered those
1966, 0.0025 0.0020 6.0012 using more than 1 pack
Germany (217). 0,0078 0.0077 0.0047 a day,

 

The authors noted that
thelr figures were cone
aiderably smaller than
those of Little et al.
(173, 174) and alyo
digagreed with thelr
data on bifurcation.

 

Little and
Radford,
1967,

U.S.A. (178).

SM cee c cee ee en 25

Pipe veveserseeres &
Ex-cigarette ...... 1
Never wcccsevecune 8

Mean Pot! levels in various epithelial tissues (pe/g wet tiseue)

Bronchial wall and gubmucosa sissseecrerseseneeceeeeerernserse 0,008
Bronchial epithelium:
Trachea .....e been center euane ve cee eet teeeeeresnseesneeees O120
Lobar bronchi ......0..-.-eaaee vceeene cerreeveseerenere O90

 
 

Segmental bifurcation ..csseccecenecccerceceereeteresnes ese ce 4,600

 
£9€

TABLE Al3.—Experiments concerning the effects of the skin painting or
subcutancous injection of cigarette smoke condensate or its constituents upon animals

 

 

  
 

 

 

Author, A. Method,
year, Animal B, Frequency and/
country, and or duration, Results Comments
reference strain Cc. Material
Wynder Car, mice A. Painting shaved skin. Percent animals with: ¢ Number in paren-
etal, LB. 3/week fur 2 years. Treatment: Papillomaat Cancert thesis represents
1963, C, Whole cigarette smoke 'Tar’ alone $9.0(81) 44.0(81) total in that
U.S.A. condensate in acetone. “Tar and croton oil .. 42.0(31) 9.7(31) experimental group.
(317). Croton oil once/week. Acetone alone . (30) (30) Skin-painting
Acetone and croton oil (14) (14) experimenta prior
to 1953 are fully
detoital in tab-
ular form in this
article.
Passey 5 different A. Painting unshaven No malignant tumore noted in cither group.
etal, mouse skin. Papilloma noted on one animal (in whole “tar group) which later regressed.
1955, straing B. 2/week for 9
England (4102). months.
(209). C. Whole “tar” or
neutral fraction.
Orretal., Mice of 2 A. Painting skin. Number animala with?
1985, stroing. B. 1 or 2/week for Treatment; Papillomas
England VR months. Nenzpyrene 1/week fullowed 4/20 at 18 months (separate greup received only
(205). C. 20 pereent cigarette by “tar' 2/week. henzpyrene and showed no tumors).

“tar’’ in acetone,
0.38 percent
benzpyrene,

“Tar’ nlone O7OU at dX months.
HOF

TaBLe A1l3.—Eaperiments concerning the effects of the skin painting or
subcutaneous injection of cigarette smoke condensate or its constituents upon animals (cont.)

 

 

 

 

 

 

 

Author, Animal A. Method,

year, and B. Frequency and/
country, strain or duration, Results Comments
reference C. Material

Wynder Mice of 4 A. Painting shaved skin. Strain Papilomas Carcinomas No tumors noted with
etal, separate B. 3/week for 80 days. 10/89 2/89 acetune alone.

1965, atrains. C. Whole condensate 22/86 12/86 Stressed

U.S.A. in acetone. differences in

(348). susceptibility of
strain.

Hamer and Outbred A. Painting unshaved Treatment: Papillomas
Woodbouse, albino skin. "Tar? 2/week oo... cece eee 1/60
1966, atrain B, Varied for 18 months. “Tar and croton oil I/week. ......, 2/30
ULS.A, tice. C, Whole ‘‘tar'’/acetone, B(a)P 3 times then ‘tar’ 2/week ..... 4/30
(126). benzpyrene {B(a)P), Bnd P B times cece eee ee eee 0/30

croton oll.

Sugiura, Rockland A. Painting unshaved Paptllomae Carcinomas
1966, Swiss skin. 16/44 12/44 {anly 44/60
U.S.A. albino B. 8/week fur 2 yenra. lived froin
(266). mice (60). ©. Whole ‘tar’, 368-696 Unya).

Graham Albino New A. Printing shaved akin. Treatment: Papillomas Carcinomas The suthors review
etal, Zealand B. 3/week for 6 years. Condensate ooccccscceseeerecceueavnee 4l/at 6/4t previous experiments
1957, rabbits. C. Whole condensate. Condensate and eruton oi! 1/week. 10/10 2/10 with rabbits in
U.S.A, Crotun ail and acetone 1/week. 0/3 0/3 tabulur form,
(101), Acetone T/week vcssscce cet renee anes 0/7 0/7 ‘

Guerin and Mice A. Palnting neck skin, Original mumber Survivora Pupillomas Sarcomas ¢ Control group.
Curin, (Pasteur DB. 2/week for D1 your. {C. 42 wi... , ol O/iL 0/51 t Experimental group,
a wlruin,) C. Whole condensate. PELOT2 vee 220 10/220 6/220

SA,

(108),
S9E

TABLE Al3,—Experiments concerning the effects of the skin painting or

subcutaneous injection of cigarette smoke condensate or ils constituents upon animals (cont.)

 

 

 

 

 

 

 

Author, Animal A. Method,
year, an R. Frequency and/
country, wtrain or duration, Reaults Comments
reference C. Material
Wynder Swiss mice A. Painting skin. Pereent Percent
etal, B. Varicd for 12 Treatment; Number papillomas carcinomas
1957, months, 5/ week 50 12.0 8.0
U.S.A. C. Whole condensate 3/week 50 38.0 16.0
($23), in acetone. 2/week 40 10,0 3.0
1/week 40 6.0
Wynder and CAF, or A. Painting shaved skin. Percent Percent Swiss mice noted
Wright Swiss B. 3/week for lifespan. Treatment CAF,: Number papillomaa carcinomas to be more sus-
1957, mice. C. Whole ‘tar’ or nicotine Whole “tar’ ...,...... 0c. ce, 30 53.0 27.0 ceptible.
USA free tar” derived Nicotine free “tar ....... 40 73,0 26.0 Majority of carcino.
($28) from pipe and Cigarette “tar" ceeers 30 30.0 30.0 Bena noted to be
cigarette tobacco. Pipe ‘tar’ oo... ccc 30 60.0 20.0 in neutral fraction
Treatment Swiss: of condensate.
Whole “tar’ oo... .c. cece 30 §3.0 10.0
Nicotine free “tar ........... 40 43.0 20.0
Cignorette ‘tor’ ...,.......,, , 30 63.0 33.0
Pipe “tar cee 39 63.0 60.0
Gelihorn, Paris RII A. Painting shaved skin. Treatment: Papillomas Carcinomas
1958, mice B. Varied for 1-2 years, Benzpyrene (twice only) .........05, 20/529 5/629
U.S.A. C. “Tar’' in acetone, Croton oi] (5/6 week) 4/26 0/26
(99), benzpyrene, “Tar (5/6 week) 3/559 2/559
croton oil. Acetone (3/0 week) .o....... cece, 0/30 0/30
“Tar” and croton oil (5/6 week) 10/175 0/175
Bock and Swiss A. Painting skin. Pereent
Moore, female B. 8/week for lifespan. Group: Number living at 6 montha Skin tumoraat C4 weeks
1959, mice C. Whole condensate Painted oo. cc ees cce cece cee 49 13.0
U.S.A. irradiation, Painted and irradiated ......... 65 44.0
(23). Irradiated oo... cee eee eee 36

 
99€

TABLE Al3.—-Experiments concerning the effects of the skin painting or
subcutaneous injection of cigarette smoke condensate or its constituents upon animals (cont.)

 

 

   

 

 

 

 

Author, Animal A. Method,
year, and B. Frequency and/
country, atraoin or duration, Results Comments
reforenee C. Material
Druckrey, Rata A. Subcutaneous Group: Surconiad t Control group.
1961, injection, tc... bev eeaye 1/75 P Experimental group,
Germany RB. i/week for 60 weeks. tke.. sae en 16/76
(78), C. Smoke condensate in
tricaprytin and
alevhol.
Bock et al., ICR Swiss A. Painting shaved skin. Survtviug Percent Percent Skin
1962, mice B. 10/week for 1 year, Treatment: at ig weeks Skin cancer neoplasia
U.S.A. C. Cigarette “tar”, Standard cigarette ............ 24/30 25.9 54.0
($2), Standard cigarette ....e..c. cee 21/30 5.0 57.0
Standard cigarette 18/30 33.0 44.0
Standard cigarette 13./30 23.0 62.0
Filter cigarette 30/30 TO 27.0
Filter elgarette 30/30 3.0 23.0
Acetone only eas 66/06 tee toe
Control cecsesaerereeee eevee 65/65
Roe, Albino mice A. Painting shaved akin. Treatment: Survivors Percent akin tumore Author canchiuded
1062, B, 3/week for 84 wecks. “Tar and 0.025 mg. BlabP wi... 26 12.0 thal cigarette
U.S.A. C. Whole emoke "tar" “Tar” and 0.06mg. B(a)P ....., 15 27.0 amoke contaln
(285). with added B(a) P "Tar and 0.25 mg. Bla)P  ....., 15 13.0 cocarcinoxens,
in acetone. “Tor and 1.25 mg. B(a)P ...... 4 64.0
Bla) P 1.25 mg. .......0, Torres ld he
Druckrey and Rats A. Subcutaneous Treatment (BP mg./week): Sarcomas
Schildbach, injection. BD cece eee b eee eee ene en te eens 26/30
1963, B. 1/week for 700 daya. 10... 14/40
Germany C. Benzpyrene in 3 8/50
(82), tricaprylin. — (solvent) 2/75

 

 
L9E

TABLE Al3.—Ewperiments concerning the effects of the skin painting or

subcutancous injection of cigarette snioke condensate or its constituents upon animals (cont.)

 

 

 

 

  

 

  

 

 

 

    

Author, A. Method,
year, Animal B. Frequency and/
country, and or duration, Results Comments
reference strain C. Material
Homburger CAF, mice A. Painting ahaved skin. Complete Perecnt Percent
etal, B, 2-3/week for 2 years, Condensate; autopsics Papillumas Carcinomae
1963, C. Various tobacco Pipe tobacco 77 35.0 15.0
U.S.A. condensates in Cigar tobacco ud 27.5 16.0
(282), acetone. Cigarette tohacco ., 82 27.0 16.0
Benzpyrene ....... tae 54 10.0 20.0
Acetone only wise ecee eee ee G2
Bock etal, Swiss ICR A. Palnting clipped skin. Percent Perecnt
1965, mice B. 10/week for 11 weeks. Percent concentration of tar gurptineg Percent cancer and
U.S.A. C. Various smoke {type cigarette): Ti weeks cancer papilloma
(£2). condenaates in 9.2 (standard) vc... eee 96.0 30.0 67.0
acetone, 8.3 (standard) ven eeedeeee 93.0 27.0 67.0
7.9 (English standard) ........ 90.0 24.0 88.0
BT (King) fee cee eee 100.0 24.0 69.0
4.0 (filter) 98.0 9.0 36.0
4.4 (filter) 100.0 10.0 41.0
2.5 (filter) 97.0 4.0 16.0
Acetone contro] tee 94.0
Untreated control 100.0
Van Duuren Swiss ICR/ A. Painting shaved akin, Cumulative number of mice with t 7,12-dimethyl-
etal, Ha mice B, Initiating agent once Initiator Promoter Payillomaa Carcinomas bend{a)anthracenc,
1966, Promoter 3/week for DMBA ...Ether tobacco lenf extract 4/20 0/20
U.S.A, 12-14 montha. O ....... Ether tobacco lenf extract a 0/20 0/20
(206), C. DMBAT, tobacco DMBA ...Choloroform tobaceu tenf extract ......ee 1/20 0/20
extracts ciga~ © ....,., Cholorefurm tobaceo leaf extract ss... 0/20 0/20
rette "tar’’ DMBA .,.Cigarette “tar” eee eae 11/20 4/20
O ......, Cigarette “tar'! 0/20 0/20
Occ ACOLONG eee cece cece cect nena 0/20 0/20

 
89E

TABLE Al3.—2Haperiments concerning the effects of the skin painting or
subcutancous injection of cigarctte smoke condensate or ita constituents upon animals (cont.)

 

 

 

 

 

Author, A. Method
yeor, Animal B. Frequency and/
country, an or duration, Results Comments
reference strain C. Material
Munozetal., Swiss ICR/ A. Painting shaved skin, Dark tobacco ‘'tar” At risk Tumore Carcinomas The authors noted
1968, 4a mice B, Varied, 4.0 percent 81 50 7 a shortened latent
ULS.A. C. Tar’ from dark - $.0 percent rare i 46 16 period for dark
and (Colombian) and Light tobacco tar: tubacco.
Colombia light (U.S.A.) 4.0 percent 95 26 6
(197), tobaccos. 8.0 percent 98 64 20
Acetone ....45 91 0 0
Davies and Albino A. Painting shaved skin, Percent of carcinoma-bearing animals at 116 weckes The authors concluded
Day, mice LB. Varied regimen, Treatment: (actual number of animals in porentheacs) that the lack of
1969, C. Cigarette and soo mg. 150 mg. 75 mo. $7.5 mg. difference in ree
Great cigar condensate, Standard cigarette ......., 20.1(29} 13.2 (10) 0.7 (1) we sults from the Arst
Britain Cigar ieee eee o 27.139) 1nd (6) 2.1(3) and third groups
(65). Cigar tobacco cigarette... .. 13.9(10) oe oe under treatment

suxweats that the
Increased tumori-
genicity of clyar
tobaceo is tue to
physical processing
(actors,
69€

TaBLE Al4.—Experimenta concerning the effect of cigarette smoke or its constituents on tissue and organ cultures

 

 

Author,
year, Tissue or
country, organ culture Material/delivery Results
reference
Bouchard Mouse tung. Tobacco amoke condensate Increased number of mitotic abnormalities in the treated cultures; particularly in
and May, perfusion for 24 hours the first 5-10 days after grafting.

1960,
France (35).

Japan (18).

Thayer and
Kenaler,
1964,

U.S.A. (275).

Berwald and

Israel (£0).

Crocker et al.,
1965,
U.S.A. (83),

Diamond,
1966,
ULS.A. (68),

Human fetal lung.

KB mammalian
tumor cells.

SWR mice and
golden hamster
embryvs,

Suckling rat
trachea in
organ culture.

Varivus con-
tinuous cell
strains
(mammalian).

and aubsequent

grafting under renal

capsule of mice.

Direct exposure to

emoke from:

a. Whole cigarettes,

b. Tabacco alone.
c. Paper alone.

Cigarette smoke
condensate applica-

tion; filtered and
unfiltered
cigarettes.

Direct application of

benzo(a)pyrene
(B(s)P).

Application of

B(a)P in acetone,

Application of

(a) P in either
dimethylsulfuxide

(DMSO) or paraffin.

Paper smoke induced the most severe changes, consisting of cytoplasmic varu-
olization and nuclear pyknosis. Also noted were a decrease in the mitotic index
and an increase in abnormal divisions, more so with paper. amoke than with
the other two.

Significant growth inhibition was shown in unfiltered smoke, Cytotoxic compo~
nents were noted in both the gas and particulate phases.

Benzo(a)pyrene caused increased cell transformation as manifeuted by:
a. Hereditary random growth pattern.
b. Progressive growth as tumors after subcutaneous injection into adults.
c, Ability to grow continuously in culture.

Treated cultures revenled cellular metaplasia, bagsnl cell hyperplasia, jucresagat
mitotic rate, and increased H-thymidine incorporation proportional to the eun-
centration of material and duration of application,

Inhibition of cell growth.

 
OLE

TabLe Al4.—Experiments concerning the cffect of cigarette smoke or its constituents on tissue and organ cullurca (cont.)

 

Author,
year,
country,
reference

Tlasue or
organ culture

Materlal/delivery

Results

 

Borenfreund et al.,
1966,

Hamster luhg
tipaue,

Application of
B(a)P in either

a. Increased appearance of new small chromosomes and telocentric chromosomca,
b. Increased ability to grow in hamater cheek pouch and there become spindle-

 

 

U.S.A. (f8). DMSO or dimethyl- cell sarcomay.
formamide.
Guimard, Chicken embryo Application of Increased mitotic activity and increased incidence of anomalous mitoses.
1966, muscular tobacco extract.
France (£10), explants.
Lasnitzkl, Mice neonatal Application of a hy- 4. Incrensed busnl cell hyperplasia and pleomorphism of newly formed cella.
1968, trachea. drocarbon-enriched b. Increased eplthelial mitosis.

England (160),

fraction of whale
amoke condensate,

 

Lasnitzki,
1968,
England (161).

Human fetal lung
in organ culture,

Application of a hy-
drocarbon-enriched
fraction of whole
smoke condensate.

a. CelluJar enlargement and promotion of growth of new bronchi,
b. Increased mitoses, bronchial epithelial hyperplasia, and squamous mctaplnsia.
c. Inhibition of stromal growth,

 

 

Chan et al., Mouse Jung Application of a. Cellular disorganization,

1969, bud embryonic B(a)P in DMSO, b. Cellular pyknosis; nuclear shape and size Irregularitics,

U.S.A. (54). cultures, c. Increased epithelial mitotic rate and decreased mesenchymal mitotic rate in

thogye cultures exposed to B(a)P versus those exposed to pyrene or DMSO.

Leuchtenberger Mouse lung Exposure to fresh amoke:

and and kidney a. Unfiltered. a. Decreased RNA production, pyknosis, and death of cells.

Leuchtenberger, tissue and b. Activated b, Similar results, but changes were of minimal severity.

1969, organ cultures. charcoal filter.

Switzerland (165),

ce. Cigarette or
elgar tobacco,

c. Similar effects as group a., but lesa severe.
TLE

TABLE Al4.—Ezperinents concerning the effect of cigarette smoke or its constituents on tissue and organ cultures (cont.)

Author,
year,
country,
reference

Crocker,
1970,
ULS.A. (62).

Tissue or
organ culture

Various organ
cultures:

a. Whole suck
ling hamster
tracheas.

b. Whole bron-
chial tubes
from late
fetal dogs

and monkeys,

Muterial/delivery

Application of
B(a)P in serum,

Results

Squamous metaplasia; frequent pleomorphic cells; dedifercntiation of eplthellum
(inhibited by Vitumin A).
cle

TaBLe AlS.—Experiments concerning the effect of the instillation or implantation of
cigarette smoke or its constituents into the tracheobronchial tree of animals

 

 

 

 

Author, A. Method

year, Animal B. Frequency and/
country, and or duration Results
reference strain C. Material

Blacklock, CB white A. Injection into 3,4-benzpyrene: Number with tumora/numbecr exposed
1957, rata. lung parenchyma a, 3 mg. in olive oi! 6/6 sarcoma.

Great by thoracotomy. b. Shing. in olive oil with dead Th bacilll 2/4 sarcoma, 4/8 squamous cell carcinoma,
Britain B. Once. e, 6.75 mg. in cholesterol pellet 1/8 squamous eell carcinoma.
(8s). C. 3,4-benzpyrene Cigarette “tar:
in olive oil, a. In olive oil 0/10,
: with dead Tb b. In olive oil with dead Tb bacilil 1/8 surcoma, t/8 squamous cell carcinoma.
bacilli or in Controls:
cholesterol, a. 0.15 ec. olive oil 0/4,
cigarette ‘“‘tar’’. b. 0.15 cc. olive oi! with dead Tb bacilli O/4,
c. Cholesterol pellets O/4,

Della Porta Syrian golden A. Direct tracheal Number of
etal, hamsters. instilllation. hamatcra with
1968, B. Weekly up to Survivors at 20 tracheobronchisl
U.S.A, 45 weeks. weeks/original carcinomas
(67), C. 1 percent 7,12-dime- Material: Weeks number expoued at death

thylbenz(a)anthra- 4, DMBA 50 yr./week ....es 45 10/20 2
cene (DMBA), b. "Tar" 200 pe. /week tenes 32 11/2i _
cigarette ‘tar’ c. DMBA FO yx./week oo... 12 9/20 -
concentrate, then ‘‘tar'’ 200.

RP WOK Core ceevees 30 _ _
d. DMBA 100 ype./week .... 17 1/20 4

e. DMBA 100 ye./week \
and ‘tar’ 500 b 20 9/20 3

pe /week visu. teeeeee el

Rigdon, White Pekin A. Intratracheal No neoplastic changes noted in either the experimental or control groups,

1960, ducks. injection,

ULS.A. Controls: 99 B. Daily for 721 days.

(ef7), Experimental C. Tobacco condensate
group: 62 lin liquid petrolatum.

 
CLE

TABLE Al$.—Experiments concerning the effect of the instillation or implantation of

cigarette smoke or tts constituents dito the tracheobronchial tree of animals (cont.)

 

 

 

 

 

 

Author, A. Method
yoar, Animal B. Frequency and/
country, and oe duration Results
reference strain C. Mnteriat
Blacklock, CL white rata. A. Inoculation at Number Percent with
1961, thoracotomy, of rats malignant tumore
Great B, Once and sacrificed Controls ..., cece scenes pet easever esses eae 276 1,5 (1 carcinoma, 3 warcomas),.
Britain at] week-2 years, Cigarette condenante 72 T1.1 (6 carcinomas, 2 sarcomas),
(25), C, Cigarette tubacco Eucerin alone 44 2.3 (1 sarcoma),
amoke condensate
in eucerin,
Herrold and  Syvian golden A. Intyatracheal Number of Number with Number of tracheoe
Dunham, hamsters, inoculation, Material: hamatera tunora bronchial tumors
1462, B. 0.6 cc./week for Ba) in Tween60 ... 6 3 & (3 papillomas, 2 carcinonina).
U.S.A, 5/6 months. Bta)P in Tween60!l 6 9 (4 papillomas, & carcinomas),
(ree), C. Benzo(a)pyrene Tweendd 6 0 _
in Tween60 B(u)P in olive oil 6 0 ~
or olive vil. Otivevil woo... 6 0 _
Rockey etal, Dogg. A, Bronchial inoculation Squamous
1962, or stimulation, Pree metaplasia
U.S.A. B. 3-5 times/week Number Invasive Carcinomas cancerous with atypicad inflam.
(224). for up to § Procedure: of doga carcinoma in atty changes changes mation
years. Controls ......,, 27 _- _ _- 6 a4
C. Cigarette smoke Manipulation of
condensate. bronchus .,.., 25 _ - _ 7 26
Smoke condensate 130 1 3 25 98 128
Tipton and Mongrel dogs. A. Bronchial Rapid induction of squamous metaplasia in condensute-exposed animals. No tabular
Crocker, Contro] group and inoculation. data is presented,
1964, experimental B. Daily for 8 days.
U,S.A. gEroup—19, C, Cigarette smoke
(277), condengate.

 
PLE

TABLE Al5.—Experiments concerning the effect of the instillation or implantation of
cigarette smoke or its constituents into the tracheobronchial tree of animals (cont.)

 

 

 

 

 

 

 

  

Author, A, Method
year, Animal B. Frequeney and/
country, and or duration Results
reference atrain C. Material
SaMiottletal., Syrian golden A. Intratracheal Percent tumor.
1966, hamsters. Inoculation. Number of bearing of Total Total number
ULS.A. B. Weekly for 15 weeks. Number autopsiad: tumor-bearing aurvivore at number of respiratory
(257), C. B(a)P (3 mg.) animals 15 weceka of tumore tract cancera
attached to fine Male ...., ete a eens 23 15 109.0 24 18
hematite duat, Female .......,, ceee TT Mt 100.0 \7 16
Kuschner, Hamsters. A. Wire mesh pellet Number of Number of
10638, implantation survivors/original animale with
U.S.A, into bronchus. Implant: number in proup lung cancer
(157), B. Lifetime, Wire mesh only vice ceccceceeccevecvece . 34/35 _
C. Bia)P, MCA ice ceca e eae 88/91 43
methylcholan- BEB) P eect eee e cece ee ener veuaens 89/91 67
threne (MCA).
SaMiottiet al, Syrian golden A. Intratracheal Number of
1968, hamsters, inoculation. hamatcra with
U.S.A, B. Weekly for 15 Number autopsied reaptratory
(235), weeks, Tnoculate: tract tumors
C. B(a)P attached Control FOE ee eet et eee tenet nnens 176 ~
toa fine B(a)Pin hematite ., fens 55 35
hematite dust. Hematite only tae 41 _
Borisyuk, Wistar rats, A. Intratracheal Number final/ Duration of
1969, intubation. tnittal inoculation
Russia B. Monthly up to Tnoculate: (monthe)
(94), 10 months, Controls eee s seca eeceesecs 11/20 12
C, Cigarette “tar”, Unfractionated ‘tar’ 24/200 10
Denicotinized “tar! oc. ccc s ee eee ee 9/45 8 (1/8 metaplasia)
Neutral “tar fraction 14/100 8 (2/14 carcinomas,

1

‘This group also received one Injection of urethane intraperitonealls,

VS papillary adenoma),
SLE

TABLE Al6.—Exrperiments concerning the effect of the inhulation of cigarette smoke

or tts constituents upon the respiratory tract of animals

(Figures in parentheses represent total pumber survivors in specific group)

 

 

Author,
year, Animal A. Type of exposure
country, and RK. Duration Results Comments
reference atrain C. Material
Lorenz ctal., Strain A mice: A. Chamber, E. Nu increase in tumor formation over that noted in controls, This strain of mice docs
1948, tC. 97, B, Up to 693 hours. haves hereditary
U.S.A. (177). TE, 97. C. Cignrette smoke,

tendency to tumor

 

 

 

 

formation.
1C. Control.
* TE. Experimental.
Essenberg, Strain A mice: A. Chamber, Percent of lung tumors No epidermoid cancer
1962, C. 32. B. 12 hours per day C. 59.4 (19) noted; papillury
U.S.A. (92), E, 36. for t year. E.. 91.3 (23) adenocarcinoma was
C. Cigarette smoke. most common
Percentage difference
is significant at
PSOUt bevel.
Mihlbock, Hybrid (020x A. Chamber, Percent with alveolur carcinomas No other type of
1955, DBA) mice: B. 2 hours per day for Cc. 31.0 lung tumors were
Netherlands C. 32, up to 684 days. E. 79.0 found,
(195), E. 29. C. Cigarette smoke.
Leuchtenberger CF, albino mice: A. Chamber, 29 of the experimental mice showed:
etal, C. and E. 276, B. To 8 cigarettes 15 busal cell hyperplasia,
1958, per day from 44 atypical basal cell hyperplasia.
ULS.A. (166), 11-201 daya, 7 dysplasia,
C. Cigarette smoke, 2 aquamous cell metaplasia.
Guerin, IC and Wistar A. Chamber, Percentage of rate with pulmonary tumors
1969, strain rats, B. 45 minutes C. 2.4 percent of 39 survivors,
France (108), C. 40. per day from E. §.1 percent of 68 survivora,
E. 100. 2-6 months.
C. Cigarette amoke.