Antioxidant activity and other mechanisms of thiols involved in chemoprevention of mutation and cancer.

Our studies provide evidence that thiols, such as N-acetyl-L-cysteine, inhibit both spontaneous mutations and induced mutations in bacteria, prevent the in vivo formation of carcinogen-DNA adducts, and suppress or delay the development of tumors or preneoplastic lesions in rodents. N-Acetylcysteine and other thiols exert antioxidant activity toward superoxide anion, hydrogen peroxide, and singlet oxygen, assessed in bacterial genotoxicity models. In addition, several other mechanisms were shown to contribute to their antimutagenic and anticarcinogenic activities, in the extracellular environment and in nontarget or target cells. These mechanisms include blocking of electrophilic metabolites and of direct-acting compounds, either of endogenous or exogenous source, modulation of several xenobiotic-metabolizing pathways, and protection of DNA-dependent nuclear enzymes. Chemoprevention of mutation and cancer by thiols is particularly useful under conditions of reduced glutathione (GSH) depletion due to toxic agents or to cancer-associated viral diseases, such as acquired immunodeficiency syndrome (AIDS) or viral hepatitis B.