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Biochemical Activation of Aryl Hydrocarbon Hydroxylase Activity, Cellular Distribution of Polynuclear Hydrocarbon Metabolites, and DNA Damage by Polynuclear Hydrocarbon Products in Human Cells in Vitro¹

Departments of Physiological Chemistry [G. E. M.] and Veterinary Pathobiology [G. E. M., J. B., D. S. Y.], The Ohio State University, Columbus, Ohio 43210, and Biology Branch, National Cancer Institute [J. A. D.], Bethesda, Maryland 20014

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 µg/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 µg/ml was ineffective. 7,12-Dimethylbenzanthracene at 6 µg/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.

It was concluded that benzo(a)pyrene can initiate all the biochemical events in human cells probably necessary to initiate transformation of human cells in vitro.

¹ This work was supported in part by Contract NO1 CP 43276.

² To whom requests for reprints should be addressed, at Department of Veterinary Pathobiology, The Ohio State University, 1900 Coffey Road, Columbus, Ohio 43210.

Received 5/27/77. Accepted 3/14/78.