Formation of 7-(4-oxobutyl)guanine in hepatic DNA of rats treated with N-nitrosopyrrolidine.
We have reported previously the formation of two structurally distinct exocyclic guanine adducts (adducts 1 and 6) in liver DNA of F344 rats treated with N-nitrosopyrrolidine (NPYR). In this study, we detected and characterized a previously unidentified guanine adduct in liver DNA of NPYR-treated rats. The structure of this adduct was established as 7-(4-oxobutyl)guanine (adduct 2) by comparison with the synthetic standard and confirmed by NaBH4 reduction to 7-(4-hydroxybutyl)guanine. The level of adduct 2 in liver DNA of F344 rats treated with 450 mg/kg of NPYR by i.p. administration was 643 +/- 9 mumol/mol guanine, approximately one-third of the level of adduct 1. This study is the first to demonstrate the in vivo formation of a formylalkyl-substituted guanine adduct by a nitrosamine.
Wang
M
M
Section of Nucleic Acid Chemistry, American Health Foundation, Valhalla, New York 10595.
Chung
F L
FL
Hecht
S S
SS
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000378:metabolism*; D003853:Deoxyribonucleosides / Q000032:analysis / Q000378:metabolism; D006147:Guanine / Q000031:analogs & derivatives* / Q000032:analysis / Q000096:biosynthesis; D006358:Hot Temperature; D006868:Hydrolysis; D008099:Liver / Q000378:metabolism*; D008297:Male; D009242:N-Nitrosopyrrolidine / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D014316:Tritium
D003853:Deoxyribonucleosides; D014316:Tritium; C077581:7-(4-oxobutyl)guanine; D006147:Guanine; D004247:DNA; D009242:N-Nitrosopyrrolidine