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Aflatoxin inhibition of template activity of rat liver chromatin

1970; Elsevier BV; Volume: 224; Issue: 2 Linguagem: Inglês

10.1016/0005-2787(70)90591-5

1879-3002

Gordon S. Edwards, Gerald N. Wogan,

Plant Toxicity and Pharmacological Properties

Investigations were conducted into the nuclear site of in vivo inhibition of rat liver RNA polymerase by aflatoxin B1 and some possible reasons for lack of similar activity in vitro. 1. The ability of chromatin isolated from livers of rats killed 30 min after injection of 0.5 mg/kg aflatoxin B1 to act as a template for RNA polymerase was determined. Polymerase activity was reduced by 28–46 % when the enzyme source was a preparation solubilized from liver of untreated rats. The ability of Escherichia coli RNA polymerase to transcribe this chromatin was unimpaired. The degree of inhibition of mammalian enzyme activity by aflatoxin B1 was approximately equivalent to that caused by 0.1 mg/kg actinomycin D in the same system. 2. The activities of RNA polymerase preparations solubilized from livers of untreated rats or from animals killed 30 min after aflatoxin treatment were compared with respect to their ability to transcribe calf thymus DNA or rat liver chromatin. The enzyme preparations from the two sources were equally active, indicating that the toxin did not exert inhibition through direct interaction with the enzyme in this system. 3. Addition of aflatoxin B1, at levels of 5–12 μg/ml of medium, to an in vitro assay system containing intact rat liver nuclei, isolated from untreated rats, did not inhibit their RNA polymerase activity. Failure of the toxin to act as inhibitor under these conditions could not be attributed to limited solubility, nor to interactions of the toxin with components of the medium. These results indicate that the inhibitory effects of aflatoxin B1 on rat liver nuclear RNA polymerase activity in vivo result from interaction of the toxin, or a metabolic derivative, with component(s) of chromatin and not from direct action on the enzyme.