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! 24. Hammond, E.C., "Life Expectancy of American Men in Relation to Their Smoking Habits," Journal of the National Cancer Institute, 43(4): 951-962, October 1969. • • N O Co W . O W 0056408.01 CD OOp fJf

Confidential Attorney Work Product Attorney-Client Privilege SMOKING & HEALTH SCIENTIFIC RESEARCH 1960 to 1969 Published Literture Copy 1 of 5 Charles R Wall Compiled by SHB October 1996

' 1. 2. 3. 4. 5. 0 6. 7. 8. 9. 10. 11. 12. - Eight and One-Half Years of Observation," In: Haenszel, W. (Editor), "Epidemiological ~ ' o 0 0056408.01 W TABLE OF CONTENTS SMOKING AND HEALTH STATE-OF-THE-ART 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. Wynder, E.L., and Bross, LJ., "A Study of Etiological Factors in Cancer of the Esophagus," Ca.~~, 14(2): 389-413, March-April 1961. Royal College of Physicians, "Smoking and Health. Summary and Report of The Royal College of Physicians of London on Smoking in Relation to Cancer of the Lung and Other Diseases," New York, Pitman Publishing Corporation, 1962, 70 pp. Wynder, E.L., Onderdonk, J., and Mantel, N., "An Epidemiological Investigation of Cancer of the Bladder," a.n r, 16(11): 1388-1407, November 1963. Auerbach, 0., Stout, A.P., Hammond, E.C., and Garfinkel, L., "Smoking Habits and Age in Relation to Pulmonary Changes," New England Journal of Medicine, 269(20): 1045-1054, November 14, 1963. Kotin, P., and 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. Haenszel, W., and 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. Doll, R., and Hill, A.B., "Mortality in Relation to Smoking: Ten Years' Observations of British Doctors, Part I," British Medical Journal, 1(5395): 1399-1410, May 30, 1964. Doll, R., and Hill, A.B., "Mortality in Relation to Smoking: Ten Years' Observations of British Doctors," Concluded, British Medical Journal, 1(5396): 1460-1467, June 6, 1964. Hammond, E.C., "Evidence on the Effects of Giving Up Cigarette Smoking," American Journal of Public Health, 55(5): 682-691, May 1965. Cobb, B.G., and Ansell, J.S., "Cigarette Smoking and Cancer of the Bladder," Journal of the American Medical Association, 193(5): 329-332, August 2, 1965. N 0 0 Kahn, H.A., "The Dom Study of Smoking and Mortality Among U.S. Veterans: Report on o

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. . 13. Rockey, E.E., and Speer, F.D., "The Ill Effects of Cigarette Smoking in Dogs," International Su;__rerv, 46(6): 520-530, December 1966. 14. 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 19, U.S. Department of Health, Education, and Welfare, U.S. Public Health Service, National Cancer Institute, January 1966, pp. 127-204. 15. Doll, R., and Hill, A.B., "Mortality of British Doctors in Relation to Smoking: Observations on Coronary Thrombosis," 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. 205-268. 16. Day, T.D., "Carcinogenic Action of Cigarette Smoke Condensate of Mouse Skin," Br. J. ncer, 21: 56-81, 1967. 17. Saffiotti, U., Cefis, F., Kolb, L.H., "A Method for the Experimental Induction of Bronchogenic Carcinoma," Cancer Research, 28: 104-124, January 1968. 18. Selikoff, I.J., Hammond, E.C., and Churg, J., "Asbestos Exposure, Smoking, and Neoplasia," Journal of the American Medical Association. 204(2): 104-110, April 8, 1968. 19. Bennington, J.L., and Laubscher, F.A., "Epidemiologic Studies on Carcinoma of the Kidney. I. Association of Renal Adenocarcinoma With Smoking," Cancer, 21(6): 1069-1071, June 1968. 20. Bross, I.D.J., and Gibson, R., "Risks of Lung Cancer in Smokers Who Switch to Filter Cigarettes," American Journal of Public Health, 58(8): 1396-1403, August 1968. 21. Montesano, R., and Saffiot6, U., "Carcinogenic Response of the Respiratory Tract of Syrian Golden Hamsters to Different Doses of Diethylnitrosamine," Cancer Research, 28: 2197- 2205, November 1968. 22. Ashley, D.J.B., and Davies, H.D., "Lung Cancer in Women," Thorax, 24: 446-450, 1969. o , co 23. Hammond, E.C., and Garf nlcel, L., "Coronary Heart Disease, Stroke, and Aortic Aneurysm. o Factors in the Etiology," Archives of Environmental Health. 19(2): 167-182, August 1969. ~ 00 0056408.01 'p

312 S.\IIDT30\ dpri! l:o r r t ~ i e. i r .. ; ~. . f ~ r . }.~. E`- - '. ~ :"`^ ~ . ~ ~ ~ .ra N I t A O .~~J~~ Frc 2 (upper). Normal ciliated V pp x{W paeudostrutified bronchinl epi[helium. Flemn[osylin and en,in. p Fre. 3 Qo,cerl. Ba!al cell hypcrpla.{u of brunchi:d mttt•u-a. Hemutox}91n and euniu. X A1p. 00 W Vol. 3•3

April 1960 EFFECTS OF SMOAt\G TOBACCO 1~,' ' ~ ~ .T..~\ T 4 md eosin. N). 'a f. % . ( YV r 4 . •XI n~ h{..n 313 Ftc• 1(upper). Squumous metaplnsia of bronchial mnco+a. Hematoxylin and eosin. X400. Fta S(louer). Atypical proliferative metaplania of bronchial mucoeu. Hematoxylin and eosin. X{00•

:1CHEd Nere re- r. after tree was and the in order > f,2cre- •d in 10 eriod of at strips ide were ut mar- contin- lobe of I bron- vere re- ove the leY means rire ap- e strips ps were wessed .' (Fig. m each toxylin d with ic acid- ,t all of -ections y, only cent of •. Thus, as they 2ments, tuse of of this the re- *ections )ertain- ng, and :harfed 0 -......~......~~ April 1960 . EFFEC"f8 OF SMOKING TOBACCO ~_. FiG. 1. Low-power view of 8n-iss roll of bronchial mucosa. The tracheal mucosa is at the center of the roll. Hernatoxylin and eusin. X 4. FISDI\GS The changes observed in the tracheo- bronchial epithelium are classified as follows: Class A-no significant change; Class B- basal cell hyperplasia; Class C-squamous metaplasia; and Class D-atypical prolifera- tive metaplasia. Class A-no significant change. The tra- chea and bronchi are lined bv several ro cs of cells in which 4 types can be readily- recognized: (1) basal rells; (2) "•Etsntzzel- len" or intermediate cells; (3) ciliated cells; and (4) goblet cells. The ratio of intermedi- 311 ate:goblet:ciliated:basal cells in the normal epithelial lining averaged 0?:0.4:10:1.6 (Fig. 2). Class B-basaf cell hyperplasia. Ba>-al cells have small, dark, round nuclei with scanty cytoplasm, and the cells lie along the tuniea propria. Hyperpla=ia of basal cells is re- garded as being pre:ent when more than 3 rows of such cells are observed. The ciliated cells are usually present, and the number of goblet cells is diminished in the incide-ed areas (Fig. 3). -Class C-sqnamons metaplasia. Thi< stage

1101.33 ~s had ;,, ta, and change Has there were _y ESamina- cell hyper- lral cells in aplasia was ,ts, and this uents of the -T8\TI YC PerCeutaCp or CueA ar- ra- 29 31 27 13 W la sro fK om:° 15 21 19 6 4 3 1 1 ~LaIN Nomber of Cues 29 2s 7 5 27 9 12 April 1960 EFFECT6 OF 61IOFI\G TOBP.CCO nIS=C R01SYUCER i CLASS IU MERIr tYCRER CIISII MIlnl4 RYG[ER 12 10 3 s ~ 19 a ~ 2 fYJ 0 m ~ ip A a C 0 Dp... a/ C:hnnp. CLASS ll MOOERRrE SrCIfCR 12 10 ~ a 3 ~ a ff. ~ a ~ 2 0 m.. ~ m ico 00 A / C 0 O.p.. aF Owrq. ttA1f IY Elr[tS/YE SMOKER Co ~ 0~0 00 A I C D D.pr.. ef Chnny. a.SS r nrE En CINR LIOR[R FIC. 6. Degree of change in bronchial mucosa related to smoking history. Only the most advanced lesion is charted in each instance. bronchial tree. Focal areas of atypical meta- plasia were observed in 9 lungs. In the excessive smokers (9 cases), only 1 had normal bronchial mucosa. Extensive basal cell hyperplasia, varying from S to 10 cells in thickness, was obsen-ed in 3 persons. Squamous mefaplasia "n-as prominent in 4, extending from the trachea to, and including, 315 the terminal bronchioles. No areas of atypi- cal metaplasia were noted. In the 6 persons grouped as cigar or pipr smokers, foci of basal cell hyperplasia Vcerc observed in each instance (Fig. 6). DLSCLS8IO\ In the group of nonsmokers, normal bronchial nwcosa was observed in 50 per