Down-regulation of Cytochrome P450 2C8 by 3-methylcholanthrene in Human Hepatocellualar Carcinoma Cell Lines

3-Methylcholanthrene (MC) is a model polycyclic aromatic hydrocarbon that induces cytochrome P450 1A1 (CYP1A1) expression. This laboratory has shown previously that aromatic hydrocarbons, which are important environmental toxicants, down-regulate the expression of rat liver CYP2C11. Recent observati...

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Main Author: Utgikar, Rucha
Other Authors: Riddick, David S.
Language:en_ca
Published: 2012
Subjects:
Online Access:http://hdl.handle.net/1807/32636
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spelling ndltd-TORONTO-oai-tspace.library.utoronto.ca-1807-326362013-04-19T20:02:57ZDown-regulation of Cytochrome P450 2C8 by 3-methylcholanthrene in Human Hepatocellualar Carcinoma Cell LinesUtgikar, Ruchadrug metabolismCYP2C804193-Methylcholanthrene (MC) is a model polycyclic aromatic hydrocarbon that induces cytochrome P450 1A1 (CYP1A1) expression. This laboratory has shown previously that aromatic hydrocarbons, which are important environmental toxicants, down-regulate the expression of rat liver CYP2C11. Recent observations also suggested that CYP2C8, a human enzyme that metabolizes antineoplastic and antidiabetic drugs, among others, is down-regulated in response to aromatic hydrocarbon exposure in primary human hepatocytes. I examined the regulation of CYP2C8 at the mRNA level by MC in two human hepatocellular carcinoma cell lines, HepG2 and HepaRG. MC down-regulated CYP2C8 mRNA levels in HepG2 cells at 24 hours and in HepaRG cells at 48 hours. CYP1A1 mRNA was induced by MC in both cell lines and HepaRG cells appeared to be more sensitive than HepG2 cells to MC-induced cytotoxicity. Further studies are warranted to define the mechanisms and functional impacts of the modulation of this important human CYP by environmental toxicants.Riddick, David S.2012-062012-08-17T17:30:49ZNO_RESTRICTION2012-08-17T17:30:49Z2012-08-17Thesishttp://hdl.handle.net/1807/32636en_ca
collection NDLTD
language en_ca
sources NDLTD
topic drug metabolism
CYP2C8
0419
spellingShingle drug metabolism
CYP2C8
0419
Utgikar, Rucha
Down-regulation of Cytochrome P450 2C8 by 3-methylcholanthrene in Human Hepatocellualar Carcinoma Cell Lines
description 3-Methylcholanthrene (MC) is a model polycyclic aromatic hydrocarbon that induces cytochrome P450 1A1 (CYP1A1) expression. This laboratory has shown previously that aromatic hydrocarbons, which are important environmental toxicants, down-regulate the expression of rat liver CYP2C11. Recent observations also suggested that CYP2C8, a human enzyme that metabolizes antineoplastic and antidiabetic drugs, among others, is down-regulated in response to aromatic hydrocarbon exposure in primary human hepatocytes. I examined the regulation of CYP2C8 at the mRNA level by MC in two human hepatocellular carcinoma cell lines, HepG2 and HepaRG. MC down-regulated CYP2C8 mRNA levels in HepG2 cells at 24 hours and in HepaRG cells at 48 hours. CYP1A1 mRNA was induced by MC in both cell lines and HepaRG cells appeared to be more sensitive than HepG2 cells to MC-induced cytotoxicity. Further studies are warranted to define the mechanisms and functional impacts of the modulation of this important human CYP by environmental toxicants.
author2 Riddick, David S.
author_facet Riddick, David S.
Utgikar, Rucha
author Utgikar, Rucha
author_sort Utgikar, Rucha
title Down-regulation of Cytochrome P450 2C8 by 3-methylcholanthrene in Human Hepatocellualar Carcinoma Cell Lines
title_short Down-regulation of Cytochrome P450 2C8 by 3-methylcholanthrene in Human Hepatocellualar Carcinoma Cell Lines
title_full Down-regulation of Cytochrome P450 2C8 by 3-methylcholanthrene in Human Hepatocellualar Carcinoma Cell Lines
title_fullStr Down-regulation of Cytochrome P450 2C8 by 3-methylcholanthrene in Human Hepatocellualar Carcinoma Cell Lines
title_full_unstemmed Down-regulation of Cytochrome P450 2C8 by 3-methylcholanthrene in Human Hepatocellualar Carcinoma Cell Lines
title_sort down-regulation of cytochrome p450 2c8 by 3-methylcholanthrene in human hepatocellualar carcinoma cell lines
publishDate 2012
url http://hdl.handle.net/1807/32636
work_keys_str_mv AT utgikarrucha downregulationofcytochromep4502c8by3methylcholanthreneinhumanhepatocellualarcarcinomacelllines
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