Cultured mouse embryos metabolize benzo[a]pyrene during early gestation: genetic differences detectable by sister chromatid exchange.
Mouse embryos explanted at 7 1/2 or 8 1/2 days of gestation were cultured in medium containing benzo[a]pyrene and supplemented with 5-bromodeoxyuridine to allow detection of sister chromatid exchanges. The murine Ah locus regulates the inducible metabolism of polycyclic hydrocarbons such as benzo[a]pyrene. A high frequency of sister chromatid exchange was induced by benzo[a]pyrene in embryos from three Ah-"responsive" inbred strains (BALB/cDub, C3H/AnfCum, and C57BL/6N); there was little or no increase in two Ah-"nonresponsive" inbred strains (AKR/J and DBA/2J). Benzo[a]pyrene also induced sister chromatid exchanges in the Ah-responsive recombinant inbred line B6NXAKN-12 but not in the Ah-nonresponsive recombinant inbred line B6NXAKN-3. Sister chromatid exchange in cultured Ah-responsive mouse embryos was thus shown to be a sensitive assay. These data provide direct evidence that genetically responsive mouse embryos (early postimplantation stage) possess the subcellular processes necessary for induction of enzymes that metabolize benzo[a]pyrene to its chemically active forms(s). Both the Ah regulatory gene product (a cytoslic receptor) and the structural gene product (inducible cytochrome P1-450) therefore appear to be functional at an early embryonic age. Furthermore, this metabolic capacity may play an important role in the damage to embryonic cells by polycyclic hydracarbons.
D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology; D001580:Benzopyrenes / Q000378:metabolism*; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D004622:Embryo, Mammalian / Q000378:metabolism*; D004790:Enzyme Induction; D005260:Female; D008297:Male; D008431:Maternal-Fetal Exchange; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics*; D009924:Organ Culture Techniques; D011247:Pregnancy; D011955:Receptors, Drug / Q000235:genetics*; D012854:Sister Chromatid Exchange; D013045:Species Specificity; D019324:beta-Naphthoflavone
D001571:Benzoflavones; D001580:Benzopyrenes; D011955:Receptors, Drug; D019324:beta-Naphthoflavone; D003577:Cytochrome P-450 Enzyme System