The basic hypothesis is that enals are important in the induction of tumors by those nitrosamines which metabolically release them. It is proposed to investigate the role(s) of endogenous enals in carcinogenesis. Four nitrosamines will be used: N-nitrose-N-n-butyl(4-hydroxybutyl)amine (BHBN), and 3-(methylnitrosamino)propionaldehyde (MNPA). These nitrosamines are carcinogenic and their structures permit enal formation by alpha-hydroxylation. First, the production of enals from metabolism of these nitrosamines will be studied. Then, the in vivo formation of DNA adducts by alkylating intermediates or by endogenous enals released during metabolism will be studied. Finally, we will examine the effect of sodium 2-mercaptoethanesulfonate, which conjugate readily with enals, on metabolism, DNA adduct formation, and tumorigenicity of these nitrosamines will be examined. The results of this study will establish whether endogenous enals are important in carcinogenesis.
