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Effect of Nitrofurans Antagonistic to 3'-Methyl-4-dimethylaminoazobenzene in Hepatocarcinogenesis and RNA Polymerase Activity of Liver Cell Nuclei in Rats¹

Research Institute for Chemobidynamics, Chiba University, Izumi-cho, Narashino, Chiba 275 [M. A., K. K., M. K., K. M.], and Department of Pathology, Faculty of Medicine, Nagoya University, Showa-ku, Nagoya, Aichi 466 [Y. T.],² Japan

The purpose of this study was to determine (a) whether the hepatocarcinogenesis in rats fed 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) could be inhibited by the simultaneous and followed feeding of two nitrofurans; (b) whether 3'-Me-DAB feeding inhibited DNA-dependent RNA polymerase activity of liver nuclei; and (c) whether the nitrofurans ameliorated 3'-Me-DAB-induced changes in RNA polymerase activity. The nitrofurans were 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide and 2-amino-5-[2-(5-nitro-2-furyl)-1-(2-furyl)vinyl-1-]-1,3,4-oxadiazole. Male Donryu rats were fed 1 or 0.5 g of 3'-Me-DAB by being maintained on a diet containing 0.06% 3'-Me-DAB or 3'-Me-DAB plus 0.2% of a nitrofuran, and then they were maintained on basal diet for 60 or 300 days, respectively. The incidence of hepatomas induced by 3'-Me-DAB was reduced to about one-fifth by the simultaneous feeding of a nitrofuran. Feeding of 3'-Me-DAB brought gradual reductions of RNA polymerase activities of liver nuclei; 65 to 80% reduction of Mn⁺⁺-(NH₄)₂SO₄-activated RNA polymerase activity and 50% reduction of the Mg⁺⁺-activated one were observed in the rats fed 3'-Me-DAB diet for more than 27 days. The reduction of RNA polymerase activity was delayed or prevented by the simultaneous feeding of a nitrofuran. The induction of hepatomas in rats fed 0.5 g 3'-Me-DAB was also retarded by the followed feeding of a nitrofuran. The followed feeding of a nitrofuran promoted the recovery of 3'-Me-DAB-induced deleterious changes in RNA polymerase activity and liver nucleic acid contents. These and associated findings indicated that the nitrofurans retarded 3'-Me-DAB carcinogenesis by exhibiting their own effect, antagonistic to 3'-Me-DAB, on rat liver.

¹ Supported by a Grant-in-Aid for Scientific Research from the Japanese Ministry of Education.

² Present address: Aichi Cancer Research Institute, Chigusa-ku, Nagoya, Aichi 464, Japan.

Received 2/ 9/74. Accepted 4/10/74.