Multiple sites of action of N-hydroxy-2-acetylaminofluorene rat hepatic nuclear transcription.
This study attempts to identify the site(s) of action of N-hydroxy-2-acetylaminofluorene (N-OH-AAF) in relation to its inhibition of rat hepatic nuclear RNA synthesis. Two hr after N-OH-AAF injection (3 mg/100 g body weight), rat hepatic nuclear synthesis and nucleolar RNA synthesis in vitro were inhibited by 60 and 80%, respectively. When total nuclear RNA polymerases were solubilized and assayed in the presence of alpha-amanitin (3.2 mug/ml), only alpha-amanitin-sensitive activity was reduced (50%) by N-OH-AAF. Diethylamino-ethyl-Sephadex column chromatography confirmed this finding and further demonstrated that RNA polymerase II was the activity selectively inhibited. Since N-OH-AAF dramatically inhibited nucleolar RNA synthesis but had little effect on RNA polymerase I activity, per se, we therefore concluded that, in addition to its direct inhibitory effect on the enzymic function of RNA polymerase II, N-OH-AAF must also cause impairment of the nucleolar DNA template function.
D000546:Amanitins / Q000494:pharmacology; D000818:Animals; D002466:Cell Nucleolus / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D002852:Chromatography, Ion Exchange; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors; D003609:Dactinomycin / Q000494:pharmacology; D005449:Fluorenes / Q000494:pharmacology*; D006881:Hydroxyacetylaminofluorene / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism*; D008297:Male; D012313:RNA / Q000096:biosynthesis*; D051381:Rats; D014158:Transcription, Genetic / Q000187:drug effects*
D000546:Amanitins; D005449:Fluorenes; D003609:Dactinomycin; D006881:Hydroxyacetylaminofluorene; D012313:RNA; D012321:DNA-Directed RNA Polymerases