The role of extrahepatic organs in the first pass metabolism of N-nitrosodibutylamine.

Abstract

The organotropism of N-nitrosodibutylamine, NDBA, a powerful carcinogen for liver, lung, esophagus and urinary bladder, depends upon dose and route of administration (Druckrey et al 1967). ω-hydroxylation products of NDBA have been shown to be selectively responsible for bladder tumors occuring after low oral doses as well as after subcutaneous administration (Okada 1984). However, in rat liver in vitro α- and ω-1-hydroxylation are the major metabolic pathways but this does not explain the prevalence of ω-hydroxylation in vivo (Janzowski et al 1982). In contrast, ω-hydroxylation is predominant in microsomes of lung and small intestine (Richter et al 1987). In addition, the high first pass metabolism of NDBA in isolated perfused rat small intestinal segments (Richter et al 1986) suggested a possible role of the gut in the organotropism of NDBA carcinogenicity.