ENHANCING AND INHIBITORY EFFECTS OF SOME STILBENE AND STEROID COMPOUNDS ON INDUCTION OF HEPATOMA IN RATS FED 3'-METHYL-4-(DIMETHYLAMINO)AZOBENZENE

  • 1 January 1978
    • journal article
    • research article
    • Vol. 69  (3) , 375-382
Abstract
Examinations were made on substances that enhance or inhibit induction of hepatoma in rats previously fed 3''-methyl-4-(dimethylamino)azobenzene (3''-Me-DAB) for a brief period. The substances tested were stilbene, 4-nitrostilbene, 4,4''-dihydroxystilbene, diethylstilbestrol, 17.beta.-estradiol and methyltestosterone. Male Donryu rats were fed 0.5 g of 3''-Me-DAB by being maintained on a diet containing 0.06% 3''-Me-DAB, and then fed 0.25 or 0.5 g of a test substance with the basal diet. Comparison of the development and yield of hepatomas indicated that 4-nitrostilbene and methyltestosterone enhanced 3''-Me-DAB carcinogenesis, whereas diethylstilbestrol and 17.beta.-estradiol retarded it. Other substances showed no such activities. The enhancement by 4-nitrostilbene and inhibition by diethylstilbestrol of 3''-Me-DAB carcinogenesis was correlated with their effect on liver nucleic acid metabolism. Feeding of 4-nitrostilbene caused a selective inhibition of Mn2+-(NH4)2SO4-activated RNA polymerase activity of liver nuclei and reduced liver RNA content. The deleterious alteration of liver RNA metabolism was followed by enhancement of incorporation of i.p.-injected 3H-thymidine into DNA of liver nuclei. Feeding of diethylstilbestrol increased tissue RNA content without effect on RNA polymerase activity of liver nuclei, and increased incorporation of 3H-thymidine into DNA. The possible implication of these results with regard to the enhancement and inhibition of hepatocarcinogenesis is discussed.