O6-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 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.
Perinatal Carcinogenesis Section, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702, USA.
S K
SK
Chhabra
V L
VL
Souliotis
J W
JW
Harbaugh
S W
SW
Krasnow
A B
AB
Jones
L M
LM
Anderson
S A
SA
Kyrtopoulos
D000818:Animals; D018736:DNA Adducts / Q000378:metabolism*; D004249:DNA Damage; D004128:Dimethylnitrosamine / Q000008:administration & dosage*; D004901:Erythrocebus patas; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D005333:Fetus / Q000737:chemistry; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D008431:Maternal-Fetal Exchange; D010920:Placenta / Q000737:chemistry; D011247:Pregnancy
D018736:DNA Adducts; D000431:Ethanol; D006147:Guanine; C008449:O-(6)-methylguanine; D004128:Dimethylnitrosamine