Effects of polychlorinated biphenyls in rat liver: Quantitative analysis of enzyme-altered foci

doi:10.1016/0041-008X(91)90251-9

Toxicology and Applied Pharmacology

Volume 111, Issue 3, December 1991, Pages 469-484

https://doi.org/10.1016/0041-008X(91)90251-9 Get rights and content

Abstract

The promotional effect of various polychlorinated biphenyls and phenobarbital on enzyme-altered lesions in the rat liver was quantified within the framework of the two-stage carcinogenesis model of Moolgavkar and colleagues. The experiment analyzed here followed an initiation-promotion protocol in which female Wistar rats were initiated with diethylnitrosamine (DEN) at 10 mg/kg body wt for 10 days followed by a 8-week period of promoter treatment with various cytochrome P450 isoenzyme inducing and noninducing compounds. This analysis included 4-monochlorobiphenyl, 2,2′,4,5′-tetrachlorobiphenyl, 3,3′,4,4′-tetrachlorobiphenyl and 3-methylcholanthrene, all administered at 150 μmol/kg body wt, and phenobarbital which was administered continuously in the diet at 0.05% until termination. Animals were killed either 1 or 9 weeks after the end of treatment and their livers were examined for enzyme histological alterations. Focal transections were classified as falling into three phenotypic categories: ATPase dominant, GGT dominant, or ATPase plus GGT (coextensive). A quantitative method was used to analyze the data consisting of the number and sizes of the focal transections. The number of cells altered by the DEN treatment and cell kinetic parameters measuring the promotional effect of the various compounds were estimated. On the basis of these estimates, we computed the number of nonextinct altered foci and their volume fraction as functions of time. We found that foci exhibiting the coextensive phenotype respond most efficiently to promoter treatment, while GGT dominant foci respond weakly to all the promoters with the exception of 3-MC. For phenobarbital, we observed a significant slowing of focal cell proliferation over time.

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Effects of polychlorinated biphenyls in rat liver: Quantitative analysis of enzyme-altered foci

Abstract

Toxicol. Appl. Pharmacol.

Biochem. Biophys. Acta

Adv. Cancer Res.

Cancer Lett.

Stat. Prob. Lett.

Cell proliferation kinetics and multistage cancer risk models

J. Natl. Cancer Inst.

Development of cytochrome P-450 altered preneoplastic and neoplastic lesions during nitrosoamine-induced hepatocarcinogenesis in the rat

Cancer Res.

Determination of the length of the histological stages of apoptosis in normal liver and in altered hepatic foci of rats

Carcinogenesis

Application of quantitative stereology to the evaluation of enzyme altered foci in rat liver

Cancer Res.

A stochastic two-stage model for cancer risk assessment. II. The number and size of premalignant clones

Risk Anal.

The phenotypic stability of altered hepatic foci: Effect of the short-term withdrawal of phenobarbital

Carcinogenesis