Detoxication enzymes and chemoprevention

Abstract

Detoxication enzymes protect cells from a wide variety of xenobiotics and endogenous toxins. Current data suggest that the balance between the Phase I carcinogen-activating enzymes and the Phase II detoxifying enzymes is critical to determining an individual's risk for cancer. Human deficiencies in Phase II enzyme activity, specifically glutathione-S-transferase (GST), have been identified and associated with increased risk for colon cancer. The increased frequency of the GST M1 null genotype among individuals with primarily smoking-related cancers has been documented. Induction of Phase II enzymes by naturally occurring or synthetic agents represents a promising strategy for cancer prevention. Both the required characteristics of potential chemopreventive agents and the role of the antioxidant response element in the monofunctional induction of Phase II enzymes have been discussed. The synthetic dithiolthione oltipraz induces a battery of Phase II enzymes and inhibits chemically induced tumors in a variety of target organs. Its ability to induce Phase II enzymes in human colon tissue and blood lymphocytes has been reported. Other promising inducers with chemopreventive activity include the isothiocyanates and polyphenols. These data collectively support the future development of Phase II enzyme inducers as clinical chemopreventive agents.