Effects of Pristane on Cytochrome P450 Isozyme Expression in Rat Tissues

Carolyn B Howard,Paul E Thomas,Shalonda B Henderson,Jacqueline Stevens,Marvin A Cuchens,Jacqueline Samuel

doi:10.3390/ijerph2005010138

Abstract

Chemical carcinogenesis studies are powerful tools to obtain information on potential mechanisms of chemical factors for malignancies. In this study Western blot analyses, using monoclonal antibodies specific for three different cytochrome P450 (CYP) isozymes (CYP1A1, CYP1A2 and CYP2B), were employed to examine the effect(s) of 3-methylcholanthrene and/or pristane (2,6,10,14-tetramethylpentadecane) on the basal and inducible levels of expression of CYP proteins within Copenhagen rat tissues. Pristane exposure led to tissue specific differences in the CYP isozymes expressed and elicited increased CYP protein expression over 3-methylcholanthrene induced levels in microsomes isolated from liver, Peyer's Patches, and thymus. Within the context of the chemical carcinogenesis model employed in this study, these observations correlated with the induction of B-cell malignancies by low doses of 3-methylcholanthrene and of thymic lymphomas by a high 3-methylcholanthrene dose. The data suggest that pristane treatment affects CYP isozyme expression. This pristane-mediated effect clearly could be a contributing factor in the chemical carcinogenesis of the previously observed lymphoid malignancies, and a possible basis for the tumor enhancing effects of pristane.

Highlights

Pristane is a ubiquitous isoprenoid which has been shown to induce B-cell plasmacytoma, following intraperitoneal administration into genetically susceptible BALB/cAnPt mice [1,2,3,4,5,6]
Within hepatic samples from untreated rats (Group 1), no CYP1A1 was detected, basal levels of CYP1A2 and CYP2B proteins were apparent
The complexity of chemical carcinogenesis has led to the notion that various regulatory systems respond to exposure to a broad range of endogenous and xenobiotic compounds which can cause cancer

Summary

Introduction

Pristane is a ubiquitous isoprenoid which has been shown to induce B-cell plasmacytoma, following intraperitoneal administration into genetically susceptible BALB/cAnPt mice [1,2,3,4,5,6]. Pristane treatment altered CYP1A activity and polyamine regulation [7], and has been shown to affect several biological responses including changes in membrane fluidity, chromatin conformation and histone protein expression [8]. Pristane elicited marked effects on transactivation of transfected genes [10,11,12,13] These activities are comparable to 12-Otetradecanoylphorbol 13-acetate (TPA), a known tumor promoter [14]. Based on the disparity of the results obtained with TPA and pristane in protein kinase C substrate phosphorylation and activation of the chloramphenicol acetyltransferase genes [10] it appears that TPA and pristane exhibit different tumor promotion mechanism(s) of action in chemical carcinogenesis. Pristane is absorbed from the gut contents, disseminates through the body, and the majority of pristane is localized to the plasma membranes [16]

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Results

Conclusion