ANTIOXIDANT ENZYMES ARE ELEVATED IN DIMETHYLBENZ[A]ANTHRACENE-INDUCED NEOPLASTIC MURINE KERATINOCYTES CONTAINING AN ACTIVE RAS(HA) ONCOGENE

Antioxidant enzyme activities and peroxidation potential were measured in primary mouse keratinocytes and neoplastic keratinocytes containing an active ras(Ha) oncooene. In neoplastic cell lines, SP-1 and 308, the activities of Cu, Zn-superoxide dismutase, catalase, and glutathione transferase were significantly elevated. The peroxidation potential was lower in cell homogenates prepared from neoplastic keratinocytes than in those prepared from normal keratinocytes Consistently, neoplastic 308 cell line was found to be more resistant than the normal keratinocytes to cytotoxicity induced by UV-B irradiation. The present study suggests that the enhanced antioxidant defense system protects the initiated cells from UV-B-induced oxidative stress, and that the enhanced enzymic antioxidant defense system is potentially a mechanism favoring the selective growth of neoplastic keratinocytes.