Mechanism of aflatoxin B1 inhibition of rat hepatic nuclear RNA synthesis.

Abstract

This paper reports the evidence for the existence of multiple sites of action of aflatoxin B1 in relation to its inhibition of rat hepatic nuclear RNA synthesis. Two hours after aflatoxin B1 injection (0.3 mg/100 g body weight), rat hepatic nuclear and nucleolar RNA synthesis, in vitro, were inhibited 70 and 90% respectively. When total nuclear free and engaged RNA polymerases were solubilized and assayed in the presence of alpha-amanitin (3.2 micrograms/ml), only alpha-amanitin-sensitive activity was reduced (50 to 70%) by aflatoxin B1. DEAE-Sephadex column chromatography confirmed this finding and further demonstrated that RNA polymerase II was the activity selectively inhibited. Since aflatoxin B1 dramatically inhibited nucleolar RNA synthesis, but had little effect on RNA polymerase I activity per se, it is concluded, therefore, that, in addition to its direct inhibitory effect on the enzymic function of RNA polymerase II, aflatoxin B1 must also cause impairment of the nucleolar DNA template function.