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Influence of "Feeder Cells" and Inducers and Inhibitors of Microsomal Mixed-Function Oxidases on Hydrocarbon-induced Malignant Transformation of Cells Derived from C3H Mouse Prostate¹

McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, Wisconsin 53706

The addition of lethally irradiated rat or mouse embryo cells (which actively metabolize polycyclic aromatic hydrocarbons) as "feeders" to G23 cells derived from mouse prostate (which metabolized hydrocarbons poorly) increased the cytotoxicity of 3-methylcholanthrene and 7,12-dimethylbenz[a]anthracene but did not affect the cytotoxicity of the K-region epoxide of 3-methylcholanthrene. The yield of malignant transformation in vitro produced by 3-methylcholanthrene was significantly increased by the addition of "feeder cells." The yield induced by 7,12-dimethylbenz[a]anthracene, however, was not affected and that induced by the K-region epoxide of 3-methylcholanthrene was markedly reduced. Lethally irradiated human skin cells (which metabolized hydrocarbons less actively than mouse prostate cells), when used as feeder cells, had no influence on hydrocarboninduced cytotoxicity and malignant transformation in G23 cells. Induction of microsomal mixed-function oxidases in G23 cells by benz[a]anthracene or 2,5-diphenyloxazole was followed by similar effects: (a) increased cytotoxicity of 3-methylcholanthrene, benz[a]anthracene, and 7,12-dimethylbenz[a] anthracene and (b) no effect on the cytotoxicity of the K-region epoxide of 3-methylcholanthrene. Such induction caused an increased yield of malignant transformation induced by 3-methylcholanthrene and benz[a] anthracene, no effect on the yield of transformation caused by 7,12-dimethylbenz[a]anthracene, and a significant reduction of transformation induced by the K-region epoxide of 3-methylcholanthrene. Inhibition of these microsomal enzymes by -naphthoflavone decreased the cytotoxicity of 3-methylcholanthrene and increased the cytotoxicity of the K-region epoxide of 3-methylcholanthrene. Such treatment completely prevented transformation produced by 3-methylcholanthrene but increased the transformation induced by the K-region epoxide of 3-methylcholanthrene.

¹ Aided in part by Grant CA 7175 from the National Cancer Institute, NIH, and by Grant E 556 from the American Cancer Society.

² Present Address: Sloan-Kettering Institute for Cancer Research, New York, N. Y.

³ American Cancer Society Professor of Oncology.

Received 10/12/71. Accepted 12/29/71.