title: Benzo[a]pyrene 4,5-oxide. Discrepancy between induction of sister chromatid exchange and binding to DNA in cultured human fibroblasts.
abstract: Benzo[a]pyrene 4,5-oxide was covalently bound to DNA of cultured human fibroblasts and caused sister chromatid exchange. The monooxygenase inhibitor alpha-napthoflavone suppressed this induction of sister chromatic exchange, but did not affect binding to DNA. Control experiments with 4-nitroquinoline 1-oxide showed that alpha-naphthoflavone does not inhibit sister chromatid exchange in general. A more likely explanation for the discrepancy between induction of sister chromatid exchange and binding to DNA is that benzo[a]pyrene 4,5-oxide itself can bind to DNA, but this binding does not lead to a significant increase in sister chromatid exchange. However benzo[a]pyrene 4,5-oxide can be oxidized by monooxygenase to yet unknown products which are potent inducers of sister chromatid exchange. An important conclusion from this is that a biological effect such as the induction of sister chromatid exchange may correlate with the exact nature of DNA binding rather than with total binding, to the point where just measuring total binding may be completely misleading if intended to detect the causes of the biological effect.
mesh_terms: D000477:Alkylating Agents; D001571:Benzoflavones / Q000494:pharmacology; D001580:Benzopyrenes / Q000494:pharmacology; D002273:Carcinogens / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D003434:Crossing Over, Genetic / Q000187:drug effects*; D004247:DNA / Q000378:metabolism; D005260:Female; D005347:Fibroblasts; D006801:Humans; D008297:Male; D012854:Sister Chromatid Exchange / Q000187:drug effects*
chemical_list: D000477:Alkylating Agents; D001571:Benzoflavones; D001580:Benzopyrenes; D002273:Carcinogens; C006707:benzo(a)pyrene 4,5-epoxide; C011512:alpha-naphthoflavone; D004247:DNA