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• W1502344605 abstract "The purpose of these experiments was to determine whether 3 hepatocarcinogens, 3′-methyl-4-dimethylaminoazobenzene (3′-Me-DAB), 4′-fluoro-4-dimethylaminoazobenzene (4′-F-DAB), and thioacetamide caused similar changes in the nuclear RNA metabolism of precancerous rat liver, and whether these changes could be distinguished from those caused by the weak hepatocarcinogen 4′-methyl-4-dimethylaminoazobenzene (4′-Me-DAB). Carcinogens were administered by intraabdominal injection or by feeding in semisynthetic diets. Their effects on nuclear RNA synthesis and nuclear RNA concentration were compared 5 days after injection or after 2, 4, and 6 weeks of feeding. Nuclei were purified and the RNA fractionated into a slowly labeling non-nucleolar nuclear (NNN) RNA fraction and a more rapidly labeling nucleolar fraction. Synthesis of RNA in these subfractions was determined by incorporation of orotic acid-6-14C and adenine-8-14C. When injected: ( a ) 3′-Me-DAB decreased incorporation of orotic acid-6-14C into both subfractions and decreased the RNA content of these subfractions; ( b ) 4′-Me-DAB increased incorporation of orotic acid-6-14C into NNN RNA, but caused no change in the RNA content of either subfraction; ( c ) thioacetamide increased the RNA content of the nucleolar fraction; and ( d ) 4′-F-DAB caused no change in either the incorporation of labeled orotic acid or in the RNA content of either subfraction. When RNA synthesis was evaluated by incorporation of adenine-8-14C, injection of 4′-Me-DAB or thioacetamide increased incorporation into NNN RNA, but only thioacetamide injections increased incorporation into nucleolar RNA. Neither 3′-Me-DAB nor 4′-F-DAB injections altered adenine-8-14C incorporation. In feeding experiments, incorporation of either labeled precursor was decreased in animals fed basal diet and the concentration of RNA in both subfractions declined throughout the 6-week feeding period. After 6 weeks, animals fed 4′-Me-DAB or 3′-Me-DAB showed decreased incorporation of orotic acid-6-14C into NNN RNA, but incorporation into nucleolar RNA was unchanged. Animals fed thioacetamide for 6 weeks showed increased incorporation of labeled orotic acid into nucleolar RNA and these increases were accompanied by increases in the RNA content of this fraction. When RNA synthesis was evaluated by incorporation of adenine-8-14C, animals fed thioacetamide or 4′-F-DAB showed increased incorporation of labeled adenine into NNN RNA, but only those animals fed thioacetamide showed increased incorporation into the nucleolar RNA. It was concluded that, within the parameters of nuclear RNA content and nuclear RNA synthesis, as determined by incorporation of labeled orotic acid or labeled adenine, no common pattern existed between the 2 hepatocarcinogens 3′-Me-DAB and 4′-F-DAB, or between these and thioacetamide. Therefore, it seemed quite likely that changes in these aspects of nuclear RNA metabolism constituted irrelevant steps toward neoplasia in rat liver." @default.
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• W1502344605 date "1968-03-01" @default.
• W1502344605 modified "2023-09-23" @default.
• W1502344605 title "Effects of hepatocarcinogens on the synthesis and content of rat liver nuclear RNA." @default.
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