Concentration-dependent inhibition of development of GGT positive foci in rat liver by the environmental contaminant di(2-ethylhexyl) phthalate.
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.
DeAngelo
A B
AB
Queral
A E
AE
Garrett
C T
CT
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002332:Carnitine O-Acetyltransferase / Q000378:metabolism; D002796:Choline Deficiency / Q000201:enzymology; D004051:Diethylhexyl Phthalate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000517:prevention & control*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010795:Phthalic Acids / Q000494:pharmacology*; D011230:Precancerous Conditions / Q000517:prevention & control*; D051381:Rats; D011919:Rats, Inbred Strains; D005723:gamma-Glutamyltransferase / Q000378:metabolism*
D004785:Environmental Pollutants; D010795:Phthalic Acids; D004051:Diethylhexyl Phthalate; D002332:Carnitine O-Acetyltransferase; D005723:gamma-Glutamyltransferase