Cigarette Smoke Induces DNA Deletions in the Mouse Embryo1

Cigarette smoking causes cancer and DNA mutations. However, longterm chronic exposure to smoke is believed to be necessary for carcinogenesis. 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 and inheritable diseases. The pink-eyed unstable (/>"") 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""/p"" mice occur by deletion of one copy of the duplicated sequence. Reversion events occurring in the embryonic premelanocytes of the developing fetus give rise to black spots on the gray fur of the offspring after birth. We investigated the effects of exposure of pregnant p°"mice to cigarette smoke and cigarette smoke condensate (CSC) on the frequency of black spots occurring in the offspring. Pregnant dams were exposed (whole body) to smoke generated by either filtered or unfiltered cigarettes for 4 h, or alternatively, mice were given a 15 mg/kg dose of CSC during their 10th day of gestation. I I'M. CO concentration, and 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 smoke following a single exposure of only 4 h.