Inhibitory Effect of Antioxidants Ethoxyquin and 2(3)-tert-Butyl-4-hydroxyanisole on Hepatic Tumorigenesis in Rats Fed Ciprofibrate, a Peroxisome Proliferator

M. Sambasiva Rao, Narendra D. Lalwani, Thomas K. Watanabe, Janardan K. Reddy*

*Corresponding author for this work

Research output: Contribution to journalArticle

120 Scopus citations

Abstract

The objective of this study was to test the hypothesis that hepatocarcinogenesis by peroxisome proliferators, a novel class of chemical carcinogens, is mediated either directly by carcinogenic H202, generated by peroxisomal oxidase(s) or indirectly by free radicals produced from H202, and that antioxidants could retard or inhibit neoplasia by scavenging active oxygen (superoxide radicals 02-, hydrogen peroxide, hydroxyl radicals HO., and singlet oxygen 102). Accordingly, the effect of synthetic antioxidants 2(3)-tert-butyl-14-hydroxyanisole and ethoxyquin on the peroxisome proliferator 2-[4-(2,2-dichlorocyclopro-pyl)phenoxy]2-methyl-propionic acid (ciprofibrate)-induced hepatic tumorigenesis has been examined in male Fischer 344 rats. Rats were fed either a 2(3tert-butyl-4-hydroxyanisole (0.5% w/w)- or ethoxyquin (0.5% w/w)-containing diet with or without ciprofibrate (10 mg/kg of body weight) for 60 weeks. Rats fed ciprofibrate (10 mg/kg of body weight) in the diet or fed a diet with no added chemicals served as controls. Results of this study demonstrated that ethoxyquin markedly inhibited the hepatic tumorigenic effect of ciprofibrate, as evidenced by a decreased incidencel of tumors, a decreased number of tumors per liver, and a reduced tumor size. 2(3)-tert-Butyl-4-hydroxyanisole also caused a significant decrease in the incidence and number of hepatocellular carcinomas that were larger than 5 mm. The present data suggest that the inhibitory effect of antioxidants on ciprofibrate-induced hepatic tumorigenesis may be due to H202 and free radical-scavenging property of ethoxyquin and 2(3)-tert-butyl-4-hydroxyanisole, since these antioxidants do not prevent peroxisome proliferation and induction of H202-generating peroxisomal enzymes in livers of rats fed ciprofibrate. Whether the inhibitory effect of antioxidants is exercised on the presumptive H202 initiation process and/or on the postinitiation growth phase of foci and nodules in liver is, at present, unknown.

Original languageEnglish (US)
Pages (from-to)1072-1076
Number of pages5
JournalCancer Research
Volume44
Issue number3
StatePublished - Mar 1 1984

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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