Quantitative image cytometry of hepatocytes expressing gamma-glutamyl transpeptidase and glutathione S-transferase in diethylnitrosamine-initiated rats treated with phenobarbital and/or phthalate esters.

Authors: Carter JH; Richmond RE; Carter HW; Potter CL; Daniel FB; DeAngelo AB

Abstract: Image cytometry was used to quantify the volume of liver expressing two histochemical markers associated with neoplasia, gamma-glutamyl transpeptidase (GGT) and the placental isozyme of glutathione S-transferase (GST-P). Rats were treated with diethylnitrosamine (DENA) followed by phenobarbital (PB), di(2-ethylhexyl)phthalate (DEHP), or di-n-octyl-phthalate (DOP) for 26 weeks. In one series, PB-treated rats were given 2.0%, 0.5%, or 0.1% DEHP in the feed. GGT expression was detected diffusely throughout the liver parenchyma in several treatment groups so that any enhanced expression in altered foci (AF) and nodules (N) was not apparent. GST-P was detected only in AF and N. GST-P may represent a second genetic alteration, as GST-P+ AF and N also expressed GGT but not the reverse. The peroxisome proliferator DEHP inhibited expression of GGT or GST-P in livers of either DENA-treated or DENA+PB-treated rats. With GST-P the reduction was correlated to a reduced number of AF and N. In contrast, DEHP's stereoisomer, DOP, was as effective as PB in promoting expression of both markers. We conclude that image cytometry of hepatocytes expressing GST-P can be used in the bioassay of the carcinogenic potential of chemicals that affect liver proliferation.

Keywords: Animals; Carcinogens/*pharmacology; Diethylhexyl Phthalate/pharmacology; Diethylnitrosamine/pharmacology; Glutathione Transferase/*metabolism; Histocytochemistry; *Image Processing, Computer-Assisted; Immunoenzyme Techniques; Liver/cytology/*drug effects/enzymology; Male; Phenobarbital/pharmacology; Phthalic Acids/pharmacology; Rats; Rats, Inbred F344; Tumor Markers, Biological/analysis; gamma-Glutamyltransferase/*metabolism
Journal: The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society
Volume: 40
Issue: 8
Pages: 1105-15
Date: Aug. 1, 1992
PMID: 1352315
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Citation:

Carter JH, Richmond RE, Carter HW, Potter CL, Daniel FB, DeAngelo AB (1992) Quantitative image cytometry of hepatocytes expressing gamma-glutamyl transpeptidase and glutathione S-transferase in diethylnitrosamine-initiated rats treated with phenobarbital and/or phthalate esters. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 40: 1105-15.



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