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I I ! I I I I I ! I I I I I I I I I #~1 AUTHOR: NGUYEN, DINH TAM AND DAVID KEAST DATE: 1986 TITLE: EFFECTS OF CHRONIC DAILY EXPOSURE TO TOBACCO SMOKE ON THE HIGH LEUKEMIC AKR STRAIN OF MICE CITATION: CANCER RESEARCH 46, 3334-3340 (1986} STUDY DESIGN: Male and female inbred AKR strain of mice were either daily exposed 5 days/wk to fresh tobacco smoke from 30 cigarettes in a 7:1 air:smoke ratio for 7 to 9 min in a Hamburg II small animal smoking machine. A group of age matched control animals were also maintained. King size filtered cigarettes supplied by the Australian Tobacco Research Foundation were used for the smoke exposures. FINDINGS/RESULTS: Animals commencing TS exposure at 48 days of age died sooner and in greater numbers than in age-matched controls whether they were males or females. However, a proportion of TS- exposed animals survived up to 300 days when the mortality patterns were not significantly different from control animals. If female AKR mice commenced TS exposure at 56 days of age, the early mortality pattern was not seen until 250 days. In male mice the mortality pattern did not become significant until 350 days if TS exposure commenced at 56 days, when at this time the control animals were dying sooner than TS-exposed rats. If TS exposure commenced at 84 days of age this was further substantiated with animals surviving an additional 100 to 150 days. It appears that TS exposure has effectively detected two populations of leukemic animals within the AKR strain. Therefore, while early exposure to TS promotes a significant number of deaths compared to age-matched control animals up to 250-300 days of age, this does not persist in older animals, This promoter activity is delayed if animals commence TS exposure at a later time, and in males, a significant proportion survives for up to 100 to 150 days longer than age- matched controls. CONCLUSIONS; Daily exposure of high leukemic AKR strain of mice to low levels of fresh tobacco smoke (TS) produces significantly different mortality profiles associated with both the sex of the animal and the age at which TS exposure commences. Females tend to be susceptible and die sooner than males, where a significant proportion of animals survives longer than age-matched controls. This prolongation of life appears to be due to a failure of the leukemic state to be mobilized in the TS-exposed males. Exposure of both the females and the males to the TS does not induce significant immunological reactivity against the leukemic cells for several parameters tested, possibly due to a significant enhancement of suppressor activity in the serum of the chronically exposed animals over and above that which also occurs in age-matched control animals.