Lactols in hydrolysates of DNA treated with alpha-acetoxy-N-nitrosopyrrolidine or crotonaldehyde

alpha-Acetoxy-N-nitrosopyrrolidine (alpha-acetoxyNPYR) is a stable precurso r to alpha-hydroxyNPYR, the initial product of metabolism and proposed prox imate carcinogen of N-nitrosopyrrolidine (NPYR). Crotonaldehyde (2-butenal) is a metabolite of NPYR and also a mutagen and carcinogen. Both alpha-acet oxyNPYR and crotonaldehyde form DNA adducts, but these reactions have not b een completely characterized. In previous studies, we detected substantial amounts of unidentified radioactivity in hydrolysates of DNA that had been treated with radiolabeled alpha-acetoxyNPYR. In this study, we have charact erized these products as 2-hydroxytetrahydrofuran, the cyclic form of 4-hyd roxybutanal, and paraldol, the dimer of 3-hydroxybutanal. These products we re identified by comparison to standards and by conversion to 2,4-dinitroph enylhydrazones. 2-Hydroxytetrahydrofuran is the major product in neutral th ermal hydrolysates of alpha-acetoxy NPYR-treated DNA and is derived predomi nantly from N-2-(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 alpha-acetoxy NPYR, wit h DNA. Other products in hydrolysates of alpha-acetoxyNPYR-treated DNA are N-7-substituted guanines 5 and 6, cyclic N-7-C8 guanines 4, 11, and 12, and 1,N-2-propanodeoxyguanosines 9 and 10. Paraldol is a major product in hydr olysates of crotonaldehyde-treated DNA, being present in amounts 100 times greater than those of previously identified adducts 9 and 10, The results o f this study provide a more complete picture of the reactions of alpha-acet oxyNPYR with DNA and yield some new insights about possible endogenous DNA adducts formed from crotonaldehyde.