Inhibition of liver cell proliferation by dexamethasone does not prevent tumor induction by ciprofibrate in the rat liver

M. Sambasiva Rao, V. Subbarao

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1 Scopus citations


The mechanism of peroxisome proliferator-induced hepatocarcinogenesis in rats and mice remains controversial. The suggested mechanisms by which peroxisome proliferators cause tumors include oxidative stress resulting from elevated levels of hydrogen peroxide (H2O2) generating peroxisomal β- oxidation enzymes and increased cell proliferation. The objective of this study was to delineate the role of cell proliferation in ciprofibrate- induced hepatocarcinogenesis in rats in which liver cell proliferation is inhibited by concomitant administration of dexamethasone. Male Fischer 344 rats were fed a diet containing 0.025% ciprofibrate with or without dexamethasone (0.5 mg kg-1 diet) for 61 weeks. Rats fed dexamethasone alone or no added chemicals in the diet served as controls. The incidence of neoplastic nodules (NN) and hepatocellular carcinomas (HCC) was 100% in both ciprofibrate and ciprofibrate and dexamethasone groups. Interestingly, the multiplicity and the number of large tumors per liver was higher in the ciprofibrate and dexamethasone group. No hepatic tumors developed in rats fed control diets. The carcinogenicity of ciprofibrate in rats was independent of cell proliferation, as measurement of hepatocyte proliferation at 4 and 61 weeks showed a significant decrease in rats treated with dexamethasone and ciprofibrate compared to rats treated with ciprofibrate alone; whereas, the levels of peroxisomal enoyl CoA hydratase/3-hydroxyacyl-CoA dehydrogenase bifunctional enzyme mRNA was markedly increased in both the groups.

Original languageEnglish (US)
Pages (from-to)12-22
Number of pages11
JournalHepatology Research
Issue number1
StatePublished - Aug 1998


  • Hepatocellular carcinoma
  • Nongenotoxic carcinogens
  • Oxidative stress
  • Peroxisomes

ASJC Scopus subject areas

  • Hepatology
  • Infectious Diseases


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