METABOLISM OF BENZO(A)PYRENE BY VARIANT MOUSE HEPATOMA-CELLS

  • 1 January 1985
    • journal article
    • research article
    • Vol. 45  (8) , 3487-3492
Abstract
Four mouse hepatoma cell lines, a parent (Hepa-1c1c7) and three variants (MUL 12, BPrc1, and TAOc1BPrc1) which had been derived from Hepa-1c1c7 by the fluorescence-activated cell sorter, were incubated with benzo(a)pyrene [BAP], and the metabolites were analyzed by high-pressure liquid chromatography. Among these 4 cell lines, Hepa-1c1c7 and MUL12 metabolized BAP the most quickly and to the greatest extent, and BPrc1 had the weakest metabolic activity for this substrate. TAOc1BPrc1 had intermediate BAP-metabolizing activity, depending on the cell density and incubation time. At low cell density, the active variant TAOc1Bprc1 resembled the weakly active Bprc1 in accumulating a low amount of ethyl acetate-soluble metabolites in the medium while, at high cell density, TAOc1Bprc1 resembled the parent clone Hepa-1c1c7 and the highly active variant MUL12. At short incubation times, TAOc1Bprc1 also had low conjugating activity while, at longer incubation times, the conjugating activity approached that of Hepa-1c1c7 and MUL12. At low cell density, Bprc1 was able to produce phenols, but this variant did not seem to have this ability at high cell density. When the substrate concentration was 4 .mu.M and the incubation time was 24 h, .beta.-glucuronidase treatment of water-soluble metabolites released about 5.3 times more pmol of quinones compared with phenols. But when the substrate concentration was 25 nM, .beta.-glucuronidase released about 2.0 times as many phenols compared with quinones. The parent and the two more actively metabolizing variants showed differences in the peak times of accumulation of 9,10-diol and 7.8-diol of BAP, which may have implications for binding to DNA and nuclear proteins. BPrc1 has basal but not easily inducible aryl hydrocarbon hydroxylase activity, whereas Hepa-1c1c7, MUL12, and TAOc1Bprc1 have basal and inducible aryl hydrocarbon hydroxylase activity. Variants of a single parent cell ine can exhibit significant differences in the rate and extent of metabolism of BAP.

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