Differences in the covalent binding of benzo[a]pyrene, safrole, 1'-hydroxysafrole, and 4-aminobiphenyl to DNA of pregnant and non-pregnant mice.
The effects of pregnancy on the covalent binding of several carcinogens to DNA were investigated in mice. Non-pregnant or timed-pregnant (18th day of gestation) ICR mice of similar age were treated with benzo[a]pyrene (BP, 200 mumol/kg), safrole (600 mumol/kg), 1'-hydroxysafrole (400 mumol/kg), 4-aminobiphenyl (4-ABP, 800 mumol/kg), or trioctanoin (4 ml/kg) per os. Tissue DNA adduct levels at 24 h after carcinogen treatment were analyzed via a 32P-postlabeling assay. Pregnancy lowered the binding of the ultimate carcinogenic metabolite of BP, 7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE I), to liver and lung DNA by 29-41%, but not the binding of other metabolites. The binding of safrole and its proximate carcinogen, 1'-hydroxysafrole, to liver and kidney DNA was increased 2.3-3.5 fold. Pregnancy decreased the binding of 4-ABP to liver DNA by approximately 18% but increased its binding to kidney DNA by 67%. The results suggest that exposure to some genotoxic compounds, especially those requiring conjugation reactions for metabolic activation, may be more hazardous during pregnancy than in the non-pregnant state.
Lu
L J
LJ
Disher
R M
RM
Randerath
K
K
D000611:Aminobiphenyl Compounds / Q000378:metabolism; D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism; D002273:Carcinogens / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D005260:Female; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D011247:Pregnancy; D011270:Pregnancy, Animal; D012451:Safrole / Q000031:analogs & derivatives / Q000378:metabolism
D000611:Aminobiphenyl Compounds; D002273:Carcinogens; C006757:4-biphenylamine; D001564:Benzo(a)pyrene; D004247:DNA; C012376:1'-hydroxysafrole; D012451:Safrole