CIGARETTE-SMOKE INDUCES DNA DELETIONS IN THE MOUSE EMBRYO

Cigarette smoking causes cancer and DNA mutations. However, longterm c hronic exposure to smoke is believed to be necessary for carcino genes is. Here, we investigate the relationship between short-term exposure to smoke and the frequency of deletions in the mouse embryo. Deletions and other genome rearrangements are associated with carcinogenesis an d inheritable diseases, The pink-eyed unstable (p(un)) mutation in the C57BL/6J mouse is the result of internal duplication of 70 kb of DNA within the p gene. Spontaneous reversion events in homozygous p(un)/p( un) mice occur by deletion of one copy of the duplicated sequence. Rev ersion events occurring in the embryonic premelanocytes of the develop ing fetus give rise to black spots on the gray fur of the offspring af ter birth, We investigated the effects of exposure of pregnant p(un) m ice to cigarette smoke and cigarette smoke condensate (CSC) on the fre quency of black spots occurring in the offspring. Pregnant dams were e xposed (whole body) to smoke generated by either filtered or unfiltere d cigarettes for 4 h, or alternatively, mice were given a 15 mg/kg dos e of CSC during their 10th day of gestation. TPM, CO concentration, an d plasma nicotine and cotinine levels were determined to characterize the smoke exposure, There was a significant increase in the number of DNA deletions in the embryo as evidenced by spotted offspring in both smoke-exposed groups and in the CSC group. These results suggest that embryos are highly sensitive to the genotoxic activity of cigarette sm oke following a single exposure of only 4 h.