Cancer and free radicals.
It is now clear that free radical intermediates often are involved in the activation of many types of procarcinogens and promutagens to their active forms as well as in the binding of these activated species to DNA. In this chapter, a general introduction to free radical chemistry is presented, with some discussion of radical lifetimes and reactivities. Potential biological targets of radical attack include lipids, proteins, and nucleic acids, and the reactions of all three of these target molecules with radicals are discussed. Finally, the evidence linking free radical reactions with chemical carcinogenesis is reviewed. A mechanistic scheme that divides the mechanisms for activating procarcinogens into 5 types is suggested; of these, 3 types of mechanisms involve free radicals, either in the activation of the carcinogen or in its binding to DNA or both. It also is suggested that a "reverse binding" can occur in which radicals produced on the DNA backbone attack and bond to unactivated substrates, rather than activated substrates (such as radicals) attacking unactivated DNA. It is known that systems that produce superoxide can lead to the production of hydroxyl radicals and that these HO. radicals form radical sites on DNA; thus, reverse binding could occur when any species that can add to a free radical is in the vicinity of the radical-damaged DNA.
D000818:Animals; D002273:Carcinogens; D004247:DNA / Q000235:genetics; D004249:DNA Damage; D005609:Free Radicals; D006801:Humans; D007700:Kinetics; D008054:Lipid Peroxides / Q000378:metabolism; D009369:Neoplasms / Q000209:etiology*; D011506:Proteins / Q000378:metabolism; D012907:Smoking; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity
D002273:Carcinogens; D005609:Free Radicals; D008054:Lipid Peroxides; D011506:Proteins; D004247:DNA; D013755:Tetradecanoylphorbol Acetate