STUDY OF CHEMICAL CARCINOGENESIS .6. EVIDENCE FOR METABOLIC ALPHA-HYDROXYLATION OF N-NITROSOPYRROLIDINE

Abstract

Metabolic .alpha.-hydroxylation of cyclic nitrosamines is important in the activation of these compounds to their ultimate carcinogenic forms. Direct evidence for this process is presented. .alpha.-Hydroxynitrosopyrrolidine and 3-formyl-1-propanediazohydroxide, which are unstable intermediates resulting from .alpha.-hydroxylation of nitrosopyrrolidine, were generated in aqueous solution from the stable precursors .alpha.-acetoxynitrosopyrrolidine and 4-(N-carbethoxy-N-nitrosamino)butanal. The major product resulting from the decomposition of .alpha.-hydroxynitrosopyrrolidine and 3-formyl-1-propanediazohydroxide was 2-hydroxytetrahydrofuran, the cyclic hemiacetal of 4-hydroxybutyraldehyde. The same product was isolated as its dinitrophenylhydrazone derivative after incubation of rat liver microsomes with nitrosopyrrolidine and treatment of rats with nitrosopyrrolidine.