DIFFERENTIAL EFFECTS OF BETA-NAPHTHOFLAVONE AND PREGNENOLONE-16-ALPHA-CARBONITRILE ON DIMETHYLNITROSAMINE-INDUCED HEPATOCARCINOGENESIS

  • 1 January 1978
    • journal article
    • research article
    • Vol. 61  (2) , 441-449
Abstract
Administration of .beta.-naphthoflavone (.beta.-NF) or pregnenolone-16.alpha.-carbonitrile (PCN) on the hepatocarcinogenicity of dimethylnitrosamine (DMN) in male SD rats was explored. Both .beta.-NF and PCN are potent repressors of the low Michaelis constant enzymatic form of DMN-demethylase, a mixed-function oxidase that catalyzes DMN demethylation. DMN-induced hepatocarcinogenesis was inhibited by PCN and was enhanced by .beta.-NF. Liver tumors (7) were found in 45 rats fed DMN plus PCN compared to 14 liver tumors in 43 rats fed DMN alone; 32 liver tumors were found in 43 rats fed DMN plus .beta.-NF. No liver tumors were detected in rats that received only PCN, .beta.-NF or the administration vehicles. Of the 53 liver tumors observed, 53% were angiosarcomas; this type of tumor was found in all 3 groups of rats that received DMN.