BIOCHEMICAL ACTIVATION OF ARYL-HYDROCARBON HYDROXYLASE-ACTIVITY, CELLULAR DISTRIBUTION OF POLYNUCLEAR HYDROCARBON METABOLITES, AND DNA DAMAGE BY POLYNUCLEAR HYDROCARBON PRODUCTS IN HUMAN CELLS INVITRO

  • 1 January 1978
    • journal article
    • research article
    • Vol. 38  (6) , 1638-1644
Abstract
Carcinogenic polynuclear hydrocarbons [7,12-dimethylbenzanthracene, 3-methylcholanthrene and benzo(a)pyrene] were added to human skin fibroblast cell cultures. Only benzo(a)pyrene at 10 .mu.g/ml or above induced mixed function hydroxylase activity, altered cell proliferation kinetics and caused DNA damage as measured by altered grain count and bromodeoxyuridine incorporation. 3-Methylcholanthrene at concentrations as high as 15 .mu.g/ml was ineffective. 7,12-Dimethylbenzanthracene at 6 .mu.g/ml or above induced mixed function oxygenase and stimulated DNA synthesis and cell proliferation, but at those concentrations little or no cytotoxicity or DNA damage was detected. The noncarcinogenic analogs 6,8,12-trimethylbenzanthracene, 5-fluorodimethylbenzanthracene, anthracene and phenanthrene had no detectable effect on the human cells. Benzo(a)pyrene can initiate all the biochemical events in human cells probably necessary to initiate transformation of human cells in vitro.

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