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 μmol/kg), safrole (600 μmol/kg), 1′-hydroxysafrole (400 μmol/kg), 4-aminobiphenyl (4-ABP, 800 μmol/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, 7β,8α-dihydroxy-9α,10α-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 ∼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.