O-6-METHYLGUANINE DNA ADDUCT FORMATION AND MODULATION BY ETHANOL IN PLACENTA AND FETAL TISSUES AFTER EXPOSURE OF PREGNANT PATAS MONKEYS TO N-NITROSODIMETHYLAMINE

Perinatal nitrosamine exposures may contribute to childhood cancer ris k. To test primate fetal susceptibility to formation of cancer initiat ion-related DNA adducts from nitrosamines, pregnant patas monkeys were given 1.0 or 0.1 mg/kg N-nitrosodimethylamine. Appreciable levels of the promutagenic O-6-methylguanine adduct occurred in placental and fe tal liver DNA after both doses and were lower but detectable in other fetal tissues after the higher dose. Coadministered ethanol (1.6 g/kg) reduced adducts in placenta and fetal liver by one-half and increased levels in other fetal tissues to the same degree. Thus, primate place nta and fetal tissues have a significant, ethanol-modulated capacity t o activate N-nitrosodimethylamine, supporting implication of nitrosami nes in human perinatal carcinogenesis and of alcohol as a modulating f actor.