DNA damage induced by nitropyrenes in primary mouse hepatocytes and in rat H4-II-E hepatoma cells.
The capacity of nitropyrenes to cause DNA damage in primary mouse hepatocytes (C57BL/6N mice) and rat H4-II-E hepatoma cells was studied by estimating single-strand breaks using the alkaline elution technique. 1-Nitropyrene (10-200 microM) caused clear dose-dependent increases in DNA strand breaks in both cell types, whereas no increase in DNA strand breaks was observed in hepatocytes treated with 1.3-, 1,6-, 1,8-dinitropyrene, 1,3,6-trinitropyrene and 1,3,6,8-tetranitropyrene under standard assay conditions (5-20 microM 30-min incubation). However, 1,8-dinitropyrene (1,8-DNP) caused dose-dependent increases in DNA strand breaks when incubated with the H4-II-E cells for 48 h, while no single-strand breaks were observed following treatment with 1,6-dinitropyrene (1,6-DNP) under the same conditions. Neither 1,6-DNP nor 1,8-DNAP induced DNA crosslinks in the H4-II-E cells. These data indicate that substrate specificity exists in the metabolic activation of nitropyrenes in murine liver.
D000818:Animals; D002478:Cells, Cultured; D003432:Cross-Linking Reagents; D004247:DNA / Q000235:genetics; D008099:Liver / Q000187:drug effects; D008114:Liver Neoplasms, Experimental / Q000235:genetics; D051379:Mice; D009154:Mutation / Q000187:drug effects*; D011721:Pyrenes / Q000633:toxicity*; D051381:Rats
D003432:Cross-Linking Reagents; D011721:Pyrenes; D004247:DNA