Evidence for Metabolic a Hydroxylation of N-Nitrosopyrrolidine

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