Comparison of hepatic peroxisome proliferative effect and its implication for hepatocarcinogenicity of phthalate esters, di(2-ethylhexyl) phthalate, and di(2-ethylhexyl) adipate with a hypolipidemic drug

J. K. Reddy, M. K. Reddy, M. I. Usman

Research output: Contribution to journalArticle

81 Scopus citations

Abstract

Peroxisome proliferation is inducible in hepatocytes of rodent and nonrodent species by structurally dissimilar hypolipidemic drugs and certain phthalate ester plasticizers. The induction of peroxisome proliferation appears to be a tissue specific response limited largely to the hepatocyte. Peroxisome proliferation is associated with increases in the activity of the H2O2-generating peroxisomal fatty acid β-oxidation system and in the amount of peroxisome proliferation-associated 80,000 MW polypeptide (PPA-80). Chronic administration of these non-DNA damaging and nonmutagenic peroxisome proliferators to rats and mice results in the development of hepatocellular carcinomas. Comparative morphometric and biochemical data from rats treated with varying dose levels of ciprofibrate, a hypolipidemic drug, and di(2-ethylhexyl) phthalate, and di(2-ethylhexyl) adipate, the widely used plasticizers, indicate that the hepatocarcinogenic potency of these agents is correlatable with their ability to induce peroxisome proliferation, peroxisomal β-oxidation and PPA-80. Available evidence strongly favors the role of peroxisome proliferation-associated oxidative stress in the induction of liver tumors by peroxisome proliferators.

Original languageEnglish (US)
Pages (from-to)317-327
Number of pages11
JournalEnvironmental health perspectives
VolumeVOL. 65
DOIs
StatePublished - 1986

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis

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