Lactols in hydrolysates of DNA treated with α-acetoxy-n- nitrosopyrrolidine or crotonaldehyde

Mingyao Wang, Pramod Upadhyaya, Trieu T. Dinh, Leo E. Bonilla, Stephen S Hecht

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

α-Acetoxy-N-nitrosopyrrolidine (α-acetoxyNPYR) is a stable precursor to α-hydroxyNPYR, the initial product of metabolism and proposed proximate carcinogen of N-nitrosopyrrolidine (NPYR). Crotonaldehyde (2-butenal) is a metabolite of NPYR and also a mutagen and carcinogen. Both α-acetoxyNPYR and crotonaldehyde form DNA adducts, but these reactions have not been completely characterized. In previous studies, we detected substantial amounts of unidentified radioactivity in hydrolysates of DNA that had been treated with radiolabeled α-acetoxyNPYR. In this study, we have characterized these products as 2-hydroxytetrahydrofuran, the cyclic form of 4-hydroxybutanal, and paraldol, the dimer of 3-hydroxybutanal. These products were identified by comparison to standards and by conversion to 2,4-dinitrophenylhydrazones. 2-Hydroxytetrahydrofuran is the major product in neutral thermal hydrolysates of α-acetoxyNPYR-treated DNA and is derived predominantly from N2- (tetrahydrofuran-2-yl)deoxyguanosine 8. Paraldol is present to a lesser extent than 2-hydroxytetrahydrofuran in these reactions and is formed from paraldol-releasing adducts, which in turn are produced in the reaction of crotonaldehyde, a solvolysis product of α-acetoxyNPYR, with DNA. Other products in hydrolysates of α-acetoxyNPYR-treated DNA are N7-substituted guanines 5 and 6, cyclic N7-C8 guanines 4, 11, and 12, and 1,N2- propanodeoxyguanosines 9 and 10. Paraldol is a major product in hydrolysates of crotonaldehyde-treated DNA, being present in amounts 100 times greater than those of previously identified adducts 9 and 10. The results of this study provide a more complete picture of the reactions of α-acetoxyNPYR with DNA and yield some new insights about possible endogenous DNA adducts formed from crotonaldehyde.

Original languageEnglish (US)
Pages (from-to)1567-1573
Number of pages7
JournalChemical research in toxicology
Volume11
Issue number12
DOIs
StatePublished - 1998

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