O6-Methylguanine DNA adduct formation and modulation by ethanol in placenta and fetal tissues after exposure of pregnant patas monkeys to N-nitrosodimethylamine

• Published in: Cancer research (Chicago, Ill.) Vol. 55; no. 24; pp. 6017 - 6020
• Main Authors: CHHABRA, S. K, SOULIOTIS, V. L, HARBAUGH, J. W, KRASNOW, S. W, JONES, A. B, ANDERSON, L. M, KYRTOPOULOS, S. A
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15-12-1995
• Subjects: Animals; Biological and medical sciences; Carcinogenesis, carcinogens and anticarcinogens; Chemical agents; Dimethylnitrosamine - administration & dosage; DNA Adducts - metabolism; DNA Damage; Erythrocebus patas; Ethanol - administration & dosage; Female; Fetus - chemistry; Guanine - analogs & derivatives; Guanine - metabolism; Maternal-Fetal Exchange; Medical sciences; Placenta - chemistry; Pregnancy; Tumors; Ethanol; Toxicity; Liver; Nitrosamine; Monkey; Tumor initiation; Malignant tumor; In utero; Pregnancy; Carcinogen; Vertebrata; Mammalia; Placenta; Animal; DNA; Modulation; Primates; Fetus; Molecular adduct
• ISSN: 0008-5472; 1538-7445

Perinatal nitrosamine exposures may contribute to childhood cancer risk. To test primate fetal susceptibility to formation of cancer initiation-related DNA adducts from nitrosamines, pregnant patas monkeys were given 1.0 or 0.1 mg/kg N-nitrosodimethylamine. Appreciable levels of the promutagenic O6-methylguanine adduct occurred in placental and fetal 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 placenta and fetal tissues have a significant, ethanol-modulated capacity to activate N-nitrosodimethylamine, supporting implication of nitrosamines in human perinatal carcinogenesis and of alcohol as a modulating factor.