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.
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Reiners
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D001711:Biotransformation; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects*; D007370:Interferon Type I / Q000494:pharmacology*; D007633:Keratins / Q000378:metabolism*; D007700:Kinetics; D008168:Lung; D051379:Mice; D008815:Mice, Inbred Strains; D009154:Mutation
D007370:Interferon Type I; D015127:9,10-Dimethyl-1,2-benzanthracene; D007633:Keratins