IN-VITRO AFLATOXIN B-1-DNA BINDING BY MICROSOMES AND ITS MODULATION BY CYTOSOL - COMPARISON OF VARIOUS MAMMALIAN AND AVIAN LIVERS IN RELATION TO SPECIES-DIFFERENCE IN SUSCEPTIBILITY

Activation and inactivation of aflatoxin B-1 (B-1) by microsomes and c ytosol prepared from the liver of various mammalian and avian species were studied in vitro by determining the microsomal activity to bind a flatoxin to calf thymus DNA and the cytosol activity to-inhibit the ha mster microsome-mediated aflatoxin-DNA binding. The microsomal activit y to bind aflatoxin to DNA was higher in day-old duckling and female c hicken than in the other species, being similar in the male hamster, m ale chicken, both sexes of Japanese quail and laying duck, and lower i n the male rat and male mastomys than in the other species. The hamste r 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 af aflatoxin-DNA binding regardle ss of the presence or absence of GSH, suggesting that the contribution of cytosol glutathione S-transferase (GST) to B-1 detoxification is n egligible in the avian species. Nevertheless the cytosol of the avian species such as the Japanese quail and chicken showed apparent inhibit ory activity toward aflatoxin-DNA binding. Relative susceptibility of the mammalian and avian species to the toxic and carcinogenic effects of B-1 could be explained by the combined activities of microsomes and cytosol,indicating the importance of the Opposite activities of micro somes and cytosol toward aflatoxin-DNA binding in the species differen ce in susceptibility.