Short-term tests for transplacentally active carcinogens. A comparison of sister-chromatid exchange and the micronucleus test in mouse foetal liver erythroblasts.
The effectiveness of 6 chemicals (benzo[a]pyrene, (BaP), cyclophosphamide (CP), diethylnitrosamine (DEN), methyl methanesulphonate (MMS), mitomycin C (MC) and procarbazine (PC) ) as inducers of micronuclei in foetal liver and maternal bone marrow erythroblasts has been determined, and related to that of gamma-radiation. CP, DEN, MMS and PC were all more effective in the foetal liver. The induction of micronuclei and SCEs by each chemical in foetal erythroblasts after in vivo exposure was measured. When expressed as induction of sister-chromatid exchanges (SCEs) per erythroblast/induction of micronuclei per erythroblast (/microM/kg), the ratios obtained were MC 580, BaP 470, DEN 430, CP 258, MMS 140 and PC 13. The lowest doses detected as potentially genotoxic by each test in foetal liver erythroblasts are (with the exception of PC which is a relatively ineffective inducer of SCEs) similar. When isolated foetal livers were exposed in vitro, SCE dose responses to BaP, MC, MMS and PC could be directly related to those from in vivo exposure, indicating the role of the foetal liver in metabolic activation, but CP was considerably more cytotoxic. The transplacental micronucleus test, and in vivo/in vitro method for SCEs in foetal liver erythroblasts, provide sensitive, complementary assays for genotoxic effects of chemicals during prenatal life. Since foetal liver possesses greater metabolic potential than adult bone marrow, the transplacental tests respond to genotoxic agents not detected by bone-marrow systems.
D000818:Animals; D001564:Benzo(a)pyrene; D001580:Benzopyrenes / Q000633:toxicity; D003434:Crossing Over, Genetic / Q000187:drug effects*; D003520:Cyclophosphamide / Q000633:toxicity; D004052:Diethylnitrosamine / Q000633:toxicity; D004900:Erythroblasts / Q000648:ultrastructure; D005260:Female; D005333:Fetus / Q000187:drug effects*; D008099:Liver / Q000648:ultrastructure; D008431:Maternal-Fetal Exchange; D008741:Methyl Methanesulfonate / Q000633:toxicity; D051379:Mice; D008937:Mitomycins / Q000633:toxicity; D009153:Mutagens; D011247:Pregnancy; D011344:Procarbazine / Q000633:toxicity; D012854:Sister Chromatid Exchange / Q000187:drug effects*
D001580:Benzopyrenes; D008937:Mitomycins; D009153:Mutagens; D001564:Benzo(a)pyrene; D011344:Procarbazine; D004052:Diethylnitrosamine; D003520:Cyclophosphamide; D008741:Methyl Methanesulfonate