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