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Cultured mouse embryos metabolize benzo(a)pyrene during early gestation: genetic differences detectable by sister chromatid exchange

Journal Article · · Proc. Natl. Acad. Sci. U.S.A.; (United States)

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 mirine Ah locus regulates the inducible metabolism of polycyclic hydrocarbons such as benzo(a)pyrene. A high frequency of sister chromatid exchange wass 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 intwo 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-I2 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 state) possess the subcellular processes necessaryfor induction of enzymes that metabolize benzo(a)pyrene to its chemically active form(s). Both the Ah regulatory gene product (a cytosolic receptor) and the structural gene product (inducible cytochrome P/sub 1/-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 hydrocarbons.

OSTI ID:
6793270
Journal Information:
Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 77:6; ISSN PNASA
Country of Publication:
United States
Language:
English