DNA alkylation by carbon-centered radicals.
1. Over the last two decades, the prevalent view in chemical carcinogenesis has been that most free radicals do not bind to DNA. Recent studies, however, are demonstrating formation of adducts between DNA and free radicals such as hydroxyl radicals and aromatic cation radicals. 2. Within this context, we discuss the recent work from our group demonstrating DNA alkylation by carbon-centered radicals formed during biotransformation of genotoxic hydrazine derivatives both in vitro and in vivo. 3. The mutagenic potential of the identified methyl radical adduct, C8-methylguanine, is discussed, and other possible biological sources of carbon-centered radicals are presented.
Augusto
O
O
Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, Brasil.
Netto
L E
LE
Gomes
L F
LF
D000478:Alkylation; D000818:Animals; D001711:Biotransformation; D002244:Carbon / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D005609:Free Radicals / Q000378:metabolism; D005796:Genes / Q000187:drug effects; D006834:Hydrazines / Q000493:pharmacokinetics / Q000633:toxicity; D010084:Oxidation-Reduction
D005609:Free Radicals; D006834:Hydrazines; D002244:Carbon; D004247:DNA