Role of Reactive Oxygen Species and Lipid Peroxidation in Chemically Induced Toxicity and Carcinogenesis
The multiple types of reactive oxygen species and their chemistry is reviewed elsewhere in this text. Superoxide anion radical (O2 -·), hydrogen peroxide (H2O2), hydroxyl radical (HO) and singlet oxygen (1O2) have been proposed as playing important roles in the toxicity of various chemical agents. Some examples are given in Table 1. Their role is, however, highly controversial and, dependent on your point of view, can be considered as being either of major or minor importance in toxicology. Here I propose to outline some of the evidence which indicates that reactive oxygen species play an important role in the toxic effects of various chemical compounds. For example, it is now apparent that reactive oxygen species can, (1) damage DNA, so as to cause mutation and chromosomal damage; (2) initiate the peroxidation of membrane lipids; (3) oxidize cellular thiols; (4) degrade polysaccharides; and (5) inhibit key enzymes; etc. Given these findings, it does not seem too difficult to imagine that chemicals which enhance the formation of reactive oxygen species would wreak havoc in living cells. One must always remember, however, that the cells of aerobic organisms are well protected against reactive oxygen species by a battery of enzymatic and non-enzymatic antioxidant defenses (for review cf. Sies, 1985) since the conversion of dioxygen to water in the respiratory process generates O2 -·, H2O2, and HO·. Thus, reactive oxygen species are “normal” cellular metabolites in respiring cells and must be dealt with accordingly. A critical balance therefore exists between the generation and detoxication of reactive oxygen species in respiring cells.
KeywordsReactive Oxygen Species Lipid Peroxidation Tumor Promotion Sister Chromatid Exchange Redox Cycling
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