PMID: 11922910Mar 30, 2002Paper

The atherogen 3-methylcholanthrene induces multiple DNA adducts in mouse aortic smooth muscle cells: role of cytochrome P4501B1

Cardiovascular Research
Bhagavatula MoorthyK S Ramos

Abstract

3-Methylcholanthrene (MC), a polycylic aromatic hydrocarbon, induces atherogenesis in mice fed an atherogenic diet. In this study, we tested the hypothesis that MC would induce DNA adducts in mouse aortic smooth muscle cells (SMCs) and that cytochrome P4501B1 (CYP1B1) plays an important role in the activation of MC to genotoxic intermediates. Cultured SMCs were treated with MC or the vehicle dimethyl sulfoxide (DMSO), and DNA was isolated after 24 h. In some experiments, the cells were pre-treated with the CYP1B1 inhibitor 1-ethynylpyrene (EP) prior to exposure to MC. DNA adducts were determined by the 32P-postlabeling assay. Aryl hydrocarbon hydroxylase assay was measured by fluorimetry. MC induced formation of 12 DNA adducts that were not observed in DMSO-treated cells. DNA adduct formation was dose-dependent, with maximum response observed at 3 microM. Pre-treatment of cells with EP dramatically suppressed DNA adduct formation by MC. MC treatment caused induction of CYP1B1, but not CYP1A1. The induction of high levels of multiple DNA adducts in SMCs by MC suggests that SMCs have a functional enzymatic machinery capable of metabolically activating MC to genotoxic metabolites. The significant inhibition by EP of MC-induced DNA...Continue Reading

Citations

Jan 10, 2012·Toxicological Sciences : an Official Journal of the Society of Toxicology·Joanna S Kerley-HamiltonCraig R Tomlinson
Jun 1, 2004·Molecular and Cellular Biology·Cédric GouédardYannick Morel
Aug 1, 2006·Drug Metabolism Reviews·Hesham M Korashy, Ayman O S El-Kadi
Apr 11, 2007·Mutation Research·Arthur Penn, Carroll A Snyder
Jan 28, 2006·Biochemical and Biophysical Research Communications·Julien van GrevenyngheOlivier Fardel
Feb 24, 2015·International Journal of Hygiene and Environmental Health·A PullieroA Izzotti
Apr 26, 2015·Toxicological Sciences : an Official Journal of the Society of Toxicology·Bhagavatula MoorthyDanielle J Carlin
May 11, 2016·Toxicology·Eric Alejandro Rhon-CalderónAlicia Graciela Faletti
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Aug 30, 2017·Environmental Science. Processes & Impacts·Shouming ZhouJonathan P D Abbatt
Jul 7, 2007·Birth Defects Research. Part B, Developmental and Reproductive Toxicology·Mrinal K Sanyal, You-Lan Li
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Nov 13, 2019·Toxicology·Eric Alejandro Rhon CalderónAlicia Graciela Faletti
Nov 14, 2020·Clinical Science·Alexa N CarreraBeshay N Zordoky

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