In vitro Aflatoxin B1-DNA Binding by Microsomes and Its Modulation by Cytosol: Comparison of Various Mammalian and Avian Livers in Relation to Species Difference in Susceptibility

Abstract

Activation and inactivation of aflatoxin B1 (B1) by microsomes and cytosol prepared from the liver of various mammalian and avian species were studied in vitro by determining the microsomal activity to bind aflatoxin to calf thymus DNA and the cytosol activity to inhibit the hamster microsome-mediated aflatoxin-DNA binding. The microsomal activity to bind aflatoxin to DNA was higher in day-old duckling and female chicken than in the other species, being similar in the male hamster, male chicken, both sexes of Japanese quail and laying duck, and lower in the male rat and male mastomys than in the other species. The hamster cytosol inhibited the aflatoxin-DNA binding markedly in the presence of glutathione (GSH) but not at all in its absence. In contrast, the avian cytosol showed a similar level of aflatoxin-DNA binding regardless of the presence or absence of GSH, suggesting that the contribution of cytosol glutathione S-transferase (GST) to B1 detoxification is negligible in the avian species. Nevertheless the cytosol of the avian species such as the Japanese quail and chicken showed apparent inhibitory activity toward aflatoxin-DNA binding. Relative susceptibility of the mammalian and avian species to the toxic and carcinogenic effects of B1 could be explained by the combined activities of microsomes and cytosol, indicating the importance of the opposite activities of microsomes and cytosol toward aflatoxin-DNA binding in the species difference in susceptibility.