THE EFFECT OF DIET ON THE METABOLISM OF AFLATOXIN IN THE MAMMAL

Abstract

The metabolic fate of aflatoxin is of interest in connection with studies related to the mode of action of hepatotoxins in the induction of liver tumors. The ability of the toxin to interact with sub-cellular particles and the rate of excretion of the carcinogen by a particular specie, may be important in interpreting its gross effect on an animal. In some studies described in this thesis, the rate of metabolism of drugs in the normal rat and in the poisoned animal has been compared. It is a more useful information when the effect of a drug on animals under different dietary treatments are evaluated, since this will reflect susceptibility to these drugs by animals with nutritional deficiencies.

Evidence is here presented to show that rats on low protein diets are more susceptible to aflatoxin-poisoning, because they are unable to metabolise the drugs as rapidly as rats on high-protein diets. This finding is supported by histological evidence. In order to facilitate the identification of metabolic products of the aflatoxins, use was made of C14-labelled aflatoxin. This material was produced by incorporation of labeled isotopes into cultures of Aspergillus flavus on Czapek-Dox media. The utilisation of Sodium Acetate-1-C14, Sodium Acetate-2-C14, in the biogenesis of the aflatoxins is reported. After a given dose, aflatoxin or its metabolites were absent from the heart and muscles of animals examined. The other major part of the work described in this thesis consists of studies on the metabolism of labelled aflatoxins in animals fed on high or low-protein diets. Urine and bile samples obtained from experimental rats and rabbits were analysed for the presence of aflatoxins or its metabolites. Bile samples were obtained after the established of biliary fistulae. For the collection of urine samples, from animals under light anesthesia, diuresis was stimulated by implantation of a polyethylene cannula into the external jugular vein followed by an infusion of 5% mannitol in saline at 0.75ml per minute for rabbit and 0.2 ml per minute for rat.