Concentration-dependent inhibition of development of GGT positive foci in rat liver by the environmental contaminant di(2-ethylhexyl) phthalate

Environ Health Perspect. 1985 May:60:381-5. doi: 10.1289/ehp.8560381.

Abstract

The ability of di(2-ethylhexyl) phthalate (DEHP), a widely used plasticizer and environmental contaminant, to suppress development of putative preneoplastic lesions in rat liver was evaluated. gamma-Glutamyl transpeptidase-positive (GGT+) foci were initiated in the livers of Sprague-Dawley male rats with a single dose of diethylnitrosamine (DEN) following partial hepatectomy. Promotion of foci was commenced by feeding a choline-deficient diet (CD). A group of control rats was fed a choline-supplemented diet (CS). The ability of DEHP to suppress the emergence of GGT+ foci was evaluated by feeding additional groups of rats the CD diet containing either 0.1%, 0.5%, 1.0% or 2.0% DEHP. The CD diet promoted the number of GGT+ foci above levels in control livers. Inclusion of the plasticizer to the levels of 0.5%, 1.0% and 2.0% in the CD diet effectively inhibited the appearance of the foci. However, DEHP was unable to inhibit the promoting effect of the CD diet at a concentration of 0.1%. DEHP's ability to block development of GGT+ foci correlated with its ability to increase liver weight and to induce carnitine acetyltransferase (EC 2.3.1.7), a marker of peroxisome proliferation.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Body Weight / drug effects
  • Carnitine O-Acetyltransferase / metabolism
  • Choline Deficiency / enzymology
  • Diethylhexyl Phthalate / pharmacology*
  • Dose-Response Relationship, Drug
  • Environmental Pollutants / pharmacology*
  • Liver / drug effects
  • Liver / enzymology*
  • Liver / pathology
  • Liver Neoplasms, Experimental / prevention & control*
  • Male
  • Organ Size / drug effects
  • Phthalic Acids / pharmacology*
  • Precancerous Conditions / prevention & control*
  • Rats
  • Rats, Inbred Strains
  • gamma-Glutamyltransferase / metabolism*

Substances

  • Environmental Pollutants
  • Phthalic Acids
  • Diethylhexyl Phthalate
  • Carnitine O-Acetyltransferase
  • gamma-Glutamyltransferase