Journal Article

Dose-Dependent Indution of GST-P<sup>+</sup> Staining Foci by the Rat Hepatocarcinogen Methapyrilene in the Medium-Term Bioassay

D. M. HORN, W. H. JORDAN, D. C. HOLLOWAY, W. C. SMITH and F. C. RICHARDSON

in Toxicological Sciences

Volume 29, issue 2, pages 194-197
Published in print February 1996 | ISSN: 1096-6080
Published online February 1996 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/29.2.194
Dose-Dependent Indution of GST-P+ Staining Foci by the Rat Hepatocarcinogen Methapyrilene in the Medium-Term Bioassay

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Previous studies have demonstrated that methapyrilene hydrochloride (MP) is a rat-specific nongenotoxic carcinogen which induces liver tumors in a dose-dependent manner following chronic exposure in the diet. This study was conducted to determine the dose response of MP in the medium-term bioassay and to compare the response to tumor incidence. Two weeks following a single initiating dose of diethylnitrosamine (DEN), male F344 rats were administered MP at doses of 0, 62.5, 125, 250, or 1000 ppm in the diet for 6 weeks. A ½ partial hepatectomy was performed 3 weeks post-DEN. At termination, sections from the remaining three lobes were stained with GST-P antibody. Number and size of foci were measured using an image analysis system with a digitizing board. MP induced a dose-dependent increase in the number of GST-P+ foci/cm2 (0 ppm=0.85 foci/cm2; 62.5 ppm=1.29 foci/cm2; 125 ppm=1.59 foci/cm2; 250 ppm=6.55 foci/cm2; 1000 ppm=28.23 foci/cm2). A significantly greater number of foci were observed in the caudate lobe than in the anterior and posterior lobes. The size of individual foci was largely unaffected. This study demonstrates a strong correlation between foci induction and tumor incidence and suggests that this assay may have utility in predicting dose responses for the chronic bioassay.

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Subjects: Medical Toxicology ; Toxicology (Non-medical)

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