Alkylation and cleavage of DNA by carbon-centered radical metabolites

Abstract

Although carbon-centered radicals are formed during the metabolism of several genotoxic compounds, they have received little attention as DNA damaging agents. Carbon-centered radicals, however, can both cleave the DNA backbone and alkylate DNA bases, as has been demonstrated to occur in chemical and biochemical systems. Also, in vivo DNA alkylation by methyl radicals has been evidenced by isolation of C8-methylguanine in hydrolysates of DNA from rats administered 1,2-dimethylhydrazine. While most of the studies related to DNA damage by free radicals have been focused on oxyradicals, further studies on DNA alterations promoted by carbon-centered radicals may be necessary to elucidate the mechanisms of action of chemical mutagens and carcinogens.