Differential modulation of 7,12-dimethylbenz[a]anthracene metabolism in cultured keratinocytes by murine interferon-gamma.

Treatment of primary epidermal cultures derived from SENCAR mice with murine interferon-gamma (IFN-gamma) markedly inhibited keratinocyte-dependent metabolism of the promutagen 7,12-dimethylbenz[a]anthracene (DMBA). Supplementation of culture medium with 1000 U/ml of IFN-gamma, but not 10 U/ml, inhibited the rate and overall metabolism of DMBA, and the formation of water-soluble DMBA conjugants. IFN-gamma dependent effects on the formation of specific DMBA metabolites were not uniform. The kinetics of formation of DMBA phenols, and the 3,4-diol, 12-hydroxymethyl, and 7-hydroxymethyl metabolites of DMBA were similar in control, mock IFN-gamma-, and IFN-gamma-treated cultures. However, the kinetics of formation and the amounts of 8,9-diol ultimately produced were markedly reduced by IFN-gamma treatment. Collectively these data suggest that IFN-gamma differentially modulates keratinocyte metabolic processes involved in DMBA metabolism.