Subcellular distribution and covalent binding of aflatoxins as functions of dietary manipulation

Experiments were undertaken to establish the subcellular distribution and covalent binding of aflatoxin B1 (AFB1) as functions of dietary protein level and phenobarbital administration, each of which is known to modify AFB1 carcinogenicity. In addition, the effect of prior feeding of cold AFB1 on the subsequent distribution parameters for a radiolabeled dose of AFB1 was examined, since it, too, is thought to modify AFB1 responsiveness. Two dietary levels of AFB1 (2.5 and 5 ppm) were fed in combination with either a 5 or a 20% casein (5C or 20C) diet. A subgroup of animals in each experimental group was injected ip with sodium phenobarbital (PB) on 4 consecutive days prior to sacrifice. After 21 d on their respective diets, rats were given an ig dose of [3H]AFB1 and then sacrificed at various times. At the peak hours, livers from the 20C animals contained 3-6 times more radioactivity. In this group, the highest specific activities were recorded in the nuclear and microsomal fractions. The proportion of this radioactivity that was covalently bound ranged from 80 to 90% in the particulate fractions but was only 52% in the cytosol. On the other hand, the cytosol contained most of the total cellular radioactivity, most of which was loosely bound. All the experimental treatments, including feeding low-protein diets, administering PB, and feeding AFB1, reduced the total radioactivity found in the liver from a single dose of [3H]AFB1. Feeding either low-protein diets or cold AFB1 for 3 wk was associated with a higher proportion of the radioactivity as loosely bound residues. These effects are related to the lower aflatoxin carcinogenicity associated with the feeding of low-protein diets and the administration of PB.