title: Identification of C8-methylguanine in the hydrolysates of DNA from rats administered 1,2-dimethylhydrazine. Evidence for in vivo DNA alkylation by methyl radicals.
abstract: C8-Methylguanine was identified in the neutral hydrolysates of DNA isolated from the liver or colon tissue of rats administered 1,2-dimethylhydrazine. In all the samples examined, the biologically isolated adducts were characterized by co-elution with synthetic C8-methylguanine under different high pressure liquid chromatography conditions. The sample isolated from liver DNA was also identified by UV spectroscopy at different pH values and by mass spectrometry. The estimated yields of C8-methylguanine obtained in hydrolysates of DNA from the liver or colon tissue were comparable to those of O6-methylguanine. C8-Methylguanine was not detected when the spin trap alpha-(4-pyridyl-1-oxide)-N-tert- butylnitrone was administered together with 1,2-dimethylhydrazine. The spin trap also inhibited N7-methylguanine and O6-methylguanine yields, although to a lesser extent. These results constitute the first evidence that DNA alkylation by carbon-centered radicals can occur in vivo.
authors.affiliation: Department of Biochemistry, Universidade de São Paulo, Brazil.
authors.forename: L E
authors.initials: LE
authors.lastname: Netto
authors.forename: N V
authors.initials: NV
authors.lastname: RamaKrishna
authors.forename: C
authors.initials: C
authors.lastname: Kolar
authors.forename: E L
authors.initials: EL
authors.lastname: Cavalieri
authors.forename: E G
authors.initials: EG
authors.lastname: Rogan
authors.forename: T A
authors.initials: TA
authors.lastname: Lawson
authors.forename: O
authors.initials: O
authors.lastname: Augusto
mesh_terms: D019813:1,2-Dimethylhydrazine; D000478:Alkylation; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002851:Chromatography, High Pressure Liquid; D002852:Chromatography, Ion Exchange; D003106:Colon / Q000737:chemistry / Q000187:drug effects; D004247:DNA / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D004127:Dimethylhydrazines / Q000633:toxicity*; D005609:Free Radicals; D006147:Guanine / Q000031:analogs & derivatives / Q000032:analysis; D008099:Liver / Q000737:chemistry / Q000187:drug effects; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013056:Spectrophotometry, Ultraviolet
chemical_list: D002273:Carcinogens; D004127:Dimethylhydrazines; D005609:Free Radicals; C066771:8-methylguanine; D006147:Guanine; D004247:DNA; D019813:1,2-Dimethylhydrazine