Evidence for metabolic alpha hydroxylation of N-nitrosopyrrolidine

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. Both alpha-hydroxynitrosopyrrolidine and 3-formyl-1-propanediazohydroxide, which are unstable intermediates resulting from alpha hydroxylation of nitrosopyrrolidine, were generated inaqueous solution from the stable precursors alpha-acetoxynitrosopyrrolidine and 4-(N-carbethoxy-N-nitrosamino)butanal. The major product resulting from the decomposition of slpha-hydroxynitrosopyrrolidine and 3-formyl-1-propanediazohydroxide was 2-hydroxytetrahydrofuran, 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.