Hecht S S, Chen C B, Hoffmann D
Cancer Res. 1978 Jan;38(1):215-8.
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.
环状亚硝胺的代谢α-羟基化作用对于将这些化合物激活为其最终致癌形式很重要。本文提供了这一过程的直接证据。α-羟基亚硝基吡咯烷和3-甲酰基-1-丙二氮杂氢氧化物是亚硝基吡咯烷α-羟基化产生的不稳定中间体，它们在水溶液中由稳定前体α-乙酰氧基亚硝基吡咯烷和4-(N-乙氧羰基-N-亚硝基氨基)丁醛生成。α-羟基亚硝基吡咯烷和3-甲酰基-1-丙二氮杂氢氧化物分解产生的主要产物是2-羟基四氢呋喃，即4-羟基丁醛的环状半缩醛。在用亚硝基吡咯烷孵育大鼠肝微粒体后以及用亚硝基吡咯烷处理大鼠后，以其二硝基苯腙衍生物形式分离出了相同产物。
