COMPARATIVE INVITRO METABOLISM OF AFLATOXICOL BY LIVER PREPARATIONS FROM ANIMALS AND HUMANS

Abstract

The metabolism of [14C]aflatoxicol by liver postmitochondrial and microsomal fractions from humans and 8 other species was compared. A major metabolic pathway involves the dehydrogenation of aflatoxicol yielding the carcinogen aflatoxin B1. Human liver preparations were more active in this regard than preparations from any of the other species tested. Aflatoxicol dehydrogenase activity was associated with the microsomal fraction and required a H acceptor (e.g., NADP), but was not inhibited by CO, which implies that it was not dependent on the heme containing microsomal drug metabolizing system. It had a pH optimum of 8.0. Postmitochondrial liver fractions also oxidized aflatoxicol (and/or the aflatoxin B1 made from it) to at least 5 other metabolites that comigrated on TLC plates with authentic standards of aflatoxins Q1, P1, H1, M1 and B2a. None of these oxidative metabolites were formed in the presence of CO. The in vitro reduction of aflatoxin B1 to aflatoxicol by the cytosol fractions from 8 spp. was also reported. Most active in this regard were rabbit and trout preparations, while this activity was almost absent in the guinea pig. Preparations from humans and 4 other species were intermediate between these extremes.