Mechanism of Aflatoxin B, Inhibition of Rat Hepatic Nuclear RNA Synthesis*

This paper reports the evidence for the existence of multiple sites of action of aflatoxin B, in relation to its inhibition of rat hepatic nuclear RNA synthesis. Two hours after aflatoxin B, injection (0.3 mg/lOO 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 a-amanitin (3.2 pglml), only ru-amanitinsensitive activity was reduced (50 to 70%) by aflatoxin B,. DEAE-Sephadex column chromatography confirmed this finding and further demonstrated that RNA polymerase II was the activity selectively inhibited. Since aflatoxin B, 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 B, must also cause impairment of the nucleolar DNA template function.