Biochemical Activation of Aryl Hydrocarbon Hydroxylase Activity, Cellular Distribution of Polynuclear Hydrocarbon Metabolites, and DMA Damage by Polynuclear Hydrocarbon Products in Human Cells in V/fro1

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 ¿ig/mlor above induced mixed-function hydroxylase activity, altered cell prolifer ation kinetics, and caused DNA damage as measured by altered grain count and bromodeoxyuridine incorporation. 3-Methylcholanthrene at concentrations as high as 15 pg/ ml was ineffective. 7,12-Dimethylbenzanthracene at 6 /¿g/mlor above induced mixed-function oxygenase and stimulated DNA synthesis and cell proliferation, but at those concentrations little or no cytotoxicity or DNA dam age was detected. The noncarcinogenic analogs 6,8,12trimethylbenzanthracene, 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 neces sary to initiate transformation of human cells in vitro.