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! I I I I I I I I I I I I I I I ! I AUTHOR: KEAST, D., D. J. AYRE and J.M. PAPADIMTRIOU 1981 TIT~; A SURVEY OF PATHOLOGICAL CHANGES ASSOCIATED WITH LONG-TERM HIGH TAR TOBACCO SMOKE EXPOSURE IN A MURINE MODEL .CITATION= Jo PATHOLOGY, Vol. 135 (1981) 249-257 IroNed female Balb/c mice were 9 weeks old when TS-exposure commenced. I~ Control and 117 TS-exposed mice, Mice expor, ed for 7-8 minutes on 5 con~cutive da~,~",', ks for 95 wks. Fresh smoke mixed with air to achieve a 1:7 ratio, Exposure was interrupted for 3 weeks I~tween the 48 and 49~ week of exposure. Mice kd~ed for routine trials afler 70 wee~ exposure were subjected to detailed histopathological examination as were all mice stdl alive after 95 weeks exposure, Appt~ximately 16 control and 16 TS exposed mice were killed for routine trials after 56.64. 72 and ~ week~ of TS exposure, 20 Control and 10 TS-expo~d mice survived until termination of exposure, after 96 ~veeks. t li$tol.~gical examinations were conducted on I I organs .-- heart, lungs, liver, kidney, spleen, thymus, gut pancreas, brain. bladder and mu~le, plu~ any other tissue showing gross abm~rm ality. Relative mortality was expres~d a~ the actual number of control deaths ,and TS -exposed deaths multiplied by the ratio of ~urvivin$ contro~surviving TS exposed immediately prior to ~ny given death. RNDINGS/RESULTS: hong.tem~ TS.exposure of mice was found to produce a marked rise in mortality after 79 wks. After 83 weeks of TS-expt~ure lhe ~elative mortality was 1.7 time that of age-m,qtched controls. There was a sbat'p rise in overall mortality of TS-exl~ed animals between 79 and 83 wks of exposure. This parallels a significant increase in the incidence of neoplasms. The t~lative incidence of neoplasms in the TS-exposed group ~vas 3 times greater than for control groups after 83 wks exposure. By 83 wks arTS bronchial Menomas (3.8 times) and lymphomas (2.6) detected were greater in the TS e~tpm~ed than the control groups. The incidence of neoplasms, in control mice rose at a similar rate as that of TS- exposed mice between 87 and 95 wk exposure. Mice TS-exposed for 95 wks showed a greater total incidence of neoplasms than the control mice. Lymphocytic lymphomas were 3.2 times more prevalent in TS-exposed mice than the conlrol mice but bronchial adenomas have a similar incidence in b~th groups after 95 wks. A second major difference in mortality patterns between the TS -exposed mice and the controls was the incidence of large organising ovarian and papa-ovarian hematom&s. With seven being detected in the controls but only 2 in the TS exposed mice. Deaths ,qttributed to severe pneumonia was another notable difference in the mortality patterns of the TS- exl~sed mice and the controls, tlistopathological examination showed that 75% of TS-exposed mice displayed interstitial pneumonia which an classified as mild-nttxlerate or more severn while only 25% of the controls displayed similar le~ions. The incidence of other respiratory lesions was low in both groups, althou~ the incidence of focal emphysema and pulmonat7 collapse was estimated to be 2.5 times greater in the TS exposed mice. Squamous metaplasia was not detected in any of the mice. 73% of TS-exposed and 77% of the control mice presented sig~dficant palhological lesions of the liver, however the most conmaon abnom~ality was the development of a fatty change associated with ageing. The control mice were significantly more affected than the TS-exposed. One liver or panetxras associated neoplasm was obsewed in each group. The heart and thigh muscle were found to be completely flee fl'om abnormality, ,CONCL,U, SIONS: Detailed su~,'eys of grt~;s and histopathological data were presented which indicates that there is induction or H~xlucfion ~f significant numbers of malignant tumoum of several ty~s in animals exposed to tobacco smoke. There were al~o significant histc, pahological changes which consist really of interstitial pneumonia and focal low grade emphysema, These feature's contl~bute slgnificnntlyy to the reduction in life span of the test artimals in xvhich the m~in causes of death ave malignancies and inflammatot.'y diseases of the lungs.