REDOX REGULATION OF GENES THAT PROTECT AGAINST CARCINOGENS

Most carcinogens require activation to electrophilic metabolites or sp ecies that generate reactive oxygen in order to initiate the tumorigen ic process. These reactive intermediates can, in turn, be detoxified b y endogenous enzyme systems that aid in the protection of cells from e ither toxic or mutagenic product formation. The levels of many of thes e enzymes are elevated by numerous compounds found in the diet, or by antioxidants. Recent evidence describes the mechanism for this inducti on of carcinogen detoxication enzymes to be regulated at the transcrip tional level. Nuclear transcription factors bound to sites common amon g these carcinogen detoxication genes are activated by as yet unknown signal transduction pathways. The activity of these nuclear transcript ion factors are modulated by pro-and antioxidant reagents, suggesting that a redox-sensitive component governs the induction of enzymes invo lved in carcinogen metabolism. In this review, evidence for the redox regulation of the genes encoding carcinogen detoxication enzymes is pr esented. Evidence is also presented suggesting the participation of nu clear factor kappa B (NF-kappa B), mitogen-activated protein (MAP) kin ase, and basic leucine zipper (bZIP) proteins and their activation pat hways in this induction. (C) 1997 Elsevier Science Inc.