Human breast cell-mediated mutagenesis of mammalian cells by polycyclic aromatic hydrocarbons

A system has been developed in which human breast cells activate chemical procarcinogens to mutagenic compounds. The degree of activation is quantitated by the estimation of induction of 6-thioguanine-resistant specific locus mutants in a cocultured Chinese hamster V-79 cell population which does not activate carcinogens. Both mammary stromal and parenchymal cells could activate the procarcinogen 7,12-dimethylbenz(a)anthracene. In addition, it is shown that the two mammary cell populations converted both 7,12-dimethylbenz(a)anthracene and benzo(a)pyrene to water-soluble metabolites. The stromal cells produced substantial amounts of glucuronic acid conjugates, but the parenchymal cells did not. Both cell types metabolize benzo(a)pyrene to the organic-soluble metabolites 9,10- and 7,8-dihydrodiol and both 9- and 3-hydroxybenzo(a)pyrene. These results suggest that the human breast may be a target for polycyclic aromatic hydrocarbon carcinogenesis.