Distribution and metabolism of aflatoxin B1 in the marmoset monkey (Callithrix jacchus).

Abstract

Whole-body autoradiography of [3H]aflatoxin B1 (3H-AFB1) in marmoset monkeys (Callithrix jacchus) showed a localization of bound labelling, in addition to the liver, in the nasal olfactory and respiratory mucosa and the mucosa of the nasopharyngeal duct, the pharynx, the larynx, the trachea and the oesophagus. In vitro microautoradiography of these tissues incubated with 3H-AFB1 showed a localization of bound radioactivity in some cells in the epithelial linings of the tissues. This binding was abolished when the incubations were performed in the presence of the cytochrome P-450 inhibitor metyrapone. These results indicate a cytochrome P-450-dependent bioactivation of AFB1 in some structures in the epithelia of the nasal olfactory mucosa and the upper respiratory and alimentary pathways, in addition to the liver, in the marmoset monkey. Quantitation of the in vitro formation of tissue-bound radioactivity from the 3H-AFB1 showed that the nasal olfactory mucosa had the highest capacity to form bound metabolites among the tissues examined. Liquid chromatography of lipid-soluble metabolites formed by the nasal olfactory mucosa and the liver showed that aflatoxin M1 (AFM1) was the major metabolite. AFM1 was also the major metabolite found in the liver in vivo. In the pigmented tissues of the marmosets there was an accumulation of nonmetabolized AFB1. This can be related to a melanin-affinity of AFB1. The described tissues with a capacity to accumulate and metabolize AFB1 may be potential targets for the carcinogenicity of this substance in the marmoset monkey.