Hydroxylation of dibutylnitrosamine in the human liver and intestinal microsomal fractions.

Abstract

The metabolism of the bladder carcinogen N-nitroso-di-n-butylamine (NDBA) was studied in microsomal preparations of tissues of patients of both sexes, aged 59-69 years undergoing abdominal surgery. Samples of liver, ileum, and colon were of normal histological appearance. For comparison, samples of rat liver and small intestinal mucosa microsomes were included in the study. Using 1-14C-labeled NDBA, the biotransformation to hydroxylation products retaining the nitroso group, NDBA-2-OH, NDBA-3-OH, and NDBA-4-OH, respectively, was investigated by reversed phase HPLC. In order to separate these metabolites, pooled samples were analysed by normal phase HPLC. The rate of hydroxylation of NDBA was found to be 5.5 times higher in rat liver microsomes compared to those from human liver (2.86 +/- 0.29 vs 0.52 +/- 0.03 nM X min-1 X mg-1). NDBA-3-OH proved to be the major metabolite formed (greater than 80% of total metabolites). The metabolism of NDBA was low but detectable in seven out of nine specimens of human gut, 0.1-0.5 nM X mg-1 in 1 h of incubation, and of the same order of magnitude in rat intestinal tissue (0.4-0.6 nM X mg-1).