Effect of methylazoxymethanol acetate on rat liver nuclear and nucleolar RNA synthesis
Yu, F.L.; Hunter, G.; Cass, M.; Barrett, A.; Yap, T.G.; Nowicki, D.; Novak, R.
Cancer Research 43(1): 287-294
1983
ISSN/ISBN: 0008-5472 PMID: 6182991 Document Number: 207324
The effect of methylazoxymethanol acetate on rat liver nuclear and nucleolar RNA synthesis is investigated at various doses (5 to 50 mg/100 g body weight) and for various lengths of time (1 to 24 hr). The results show that this carcinogen is a potent inhibitor of both nuclear and nucleolar RNA synthesis. Like other carcinogens studied previously in this laboratory, e.g., N-hydroxy-2-acetylaminofluorene, aflatoxin B1, and actinomycin D, methylazoxymethanol acetate inhibits RNA synthesis at multiple sites. It impairs chromatin template function and selectively inhibits the activity of RNA polymerase II. Experimental evidence suggests the mechanism of inhibition of RNA polymerase II activity is due to a decrease in catalytic efficiency rather than in the total number of the enzyme. In addition, it is found that methylazoxymethanol acetate induces a dramatic condensation of nucleoplasmic chromatin.