Interferon-beta inhibits 7,12-dimethylbenz[a]anthracene-dependent mutagenesis in a keratinocyte cell-mediated mutation assay.

A cell-mediated mutagenesis assay employing cultured primary SENCAR keratinocytes for the metabolism of promutagens, and V-79 fibroblasts as target cells for the resulting genotoxic metabolites, was used to survey the effects of murine beta-interferon (IFN-beta) on 7,12-dimethylbenz[a]anthracene (DMBA) and benzo[a]pyrene (BP)-dependent mutagenesis and cytotoxicity. Pre-incubation of the keratinocyte cultures with greater than 100 units/ml IFN-beta, but not mock IFN, partially inhibited DMBA (25-60%) and BP (25-63%) dependent mutagenesis, but had little effect on the cytotoxicities of these agents. The level of inhibition was influenced by the length of keratinocyte pre-incubation with IFN-beta, and the concentration of IFN-beta, and the number of keratinocytes per nmol of promutagen. IFN-beta dependent inhibition of DMBA mutagenesis correlated with alterations in DMBA metabolism, including a decrease in the intra- and extracellular concentrations of the proximal promutagen (+/-) trans-DMBA-3,4-dihydrodiol.