Tissue-specific induction of cytochromes P450 1A1 and 1B1 by polycyclic aromatic hydrocarbons and polychlorinated biphenyls in engineered C57BL/6J mice of arylhydrocarbon receptor gene

Shimada, Tsutomu; Sugie, Atsushi; Shindo, Mitsuo; Nakajima, Taichi; Azuma, Emiko; Hashimoto, M; Inoue, Kiyoshi

doi:10.1016/s0041-008x(02)00035-2

Cited by 122 publications

(92 citation statements)

References 39 publications

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“…was used. 25,27) On the second day, the mice were sacrificed 3 h after the LPS treatment, and the liver was excised and used for total RNA isolation and microsomal preparation.…”

Section: Methodsmentioning

confidence: 99%

Effect of Lipopolysaccharide on the Xenobiotic-Induced Expression and Activity of Hepatic Cytochrome P450 in Mice

Moriya

Kataoka

Fujino

et al. 2012

Biological & Pharmaceutical Bulletin

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Infection-associated inflammation can alter the expression levels and functions of cytochrome P450s (CYPs). Cyp gene expression is regulated by the activation of several nuclear receptors, including pregnane X receptor (PXR), constitutive androstane receptor (CAR), and aryl hydrocarbon receptor (AhR). These receptors can be activated by xenobiotics, including medicines. Here, to study the xenobiotic-induced fluctuations in CYP during inflammation, we examined the effect of lipopolysaccharide (LPS) treatment on the level of mRNAs encoding hepatic CYPs induced by xenobiotic-activated nuclear receptors, in mice. Both the mRNA induction of Cyp genes and the metabolic activities of CYP proteins were examined. LPS treatment caused a significant decrease in the induced expression of the mRNAs for Cyp3a11, 2c29, 2c55, and 1a2, but not for Cyp2b10. To assess the CYP enzymatic activities, CYP3A-mediated testosterone 6β-hydroxylation and the intrinsic clearance (CL int ) of nifedipine in liver microsomes were measured in mice treated with the xenobiotic pregnenolone-16alpha-carbonitrile (PCN) with or without LPS administration. Both assays revealed that the CYP3A activity, which was induced by PCN, declined significantly after LPS treatment, and this decline correlated with the Cyp3a11 mRNA level. In addition, we found that the mRNAs for interleukin (IL)-1β and tumor necrosis factor (TNF) α were increased after treatment with LPS plus xenobiotics. Our findings demonstrated that LPS treatment reduces the PXR-and AhR-mediated, and possibly CAR-mediated Cyp gene expression and further suggest that these decreases are dependent on inflammatory cytokines in the liver.

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“…was used. 25,27) On the second day, the mice were sacrificed 3 h after the LPS treatment, and the liver was excised and used for total RNA isolation and microsomal preparation.…”

Section: Methodsmentioning

confidence: 99%

Effect of Lipopolysaccharide on the Xenobiotic-Induced Expression and Activity of Hepatic Cytochrome P450 in Mice

Moriya

Kataoka

Fujino

et al. 2012

Biological & Pharmaceutical Bulletin

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“…This leads to the up-regulation of a multitude of genes, including the cytochrome P450 isoforms CYP1A1 and CYP1B1. These enzymes metabolize their polycyclic aromatic hydrocarbon substrates to more soluble and excretable products but at the same time may activate certain metabolites into highly reactive forms (17). BaP is a classic example and is enzymatically activated to BaP-7,8-dihydrodiol-9,10-epoxide (BPDE) by cytochrome P450 enzymes.…”

mentioning

confidence: 99%

Diminished Carcinogen Detoxification Is a Novel Mechanism for Hypoxia-inducible Factor 1-mediated Genetic Instability

Schults

Timmermans

Godschalk

et al. 2010

Journal of Biological Chemistry

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The hypoxia-inducible factor 1 (HIF-1) pathway is induced in many tumors and associated with poorer outcome. The hypoxia-responsive transcription factor HIF-1␣ dimerizes with the aryl hydrocarbon receptor nuclear translocator (ARNT), which is also an important binding partner for the aryl hydrocarbon receptor (AhR). AhR is an important mediator in the metabolic activation and detoxification of carcinogens, such as the environmental pollutant benzo[a]pyrene (BaP). We hypothesized that HIF-1␣ activation attenuates BaP-induced AhR-mediated gene expression, which may lead to increased genetic instability and malignant progression. Human lung carcinoma cells (A549) were simultaneously stimulated with CoCl 2 , which leads to HIF-1␣ stabilization and varying concentrations of BaP. Both quantitative PCR and immunoblot analysis indicated that induction of the hypoxia response pathway significantly reduced the levels of AhR downstream targets CYP1A1 and CYP1B1 and AhR protein binding to ARNT. We further demonstrate that the BaP-induced hypoxanthine-guanine phosphoribosyltransferase mutation frequency and ␥-H2AX foci were markedly amplified when the HIF-1 pathway was induced. BaP-DNA adducts were only marginally increased, and transient strand breaks were diminished by HIF-1 induction, indicating changes in DNA repair. These data indicate that concurrent exposure of tumor cells to hypoxia and exogenous genotoxins can enhance genetic instability.

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“…Using male and female AhR +/+ and AhR -/-C57BL/6J mice, Shimada et al (2003a) found tissuespecific induction of CYP1A1 and 1B1 mRNAs by PAHs, 3,4,3′,4′-tetrachlorobiphenyl and the polychlorinated biphenyl mixtures, Kanechlor-300, -400 and -500. In both male and female mice, CYP1A1 mRNA was found to be constitutively expressed at very low 530 IARC MONOGRAPHS VOLUME 92 levels in various organs of AhR +/+ and AhR -/-mice and was induced in various organs by PAHs and 3,4,3′,4′-tetrachlorobiphenyl only in AhR +/+ mice.…”

Section: (Viii) Induction Of Cyp1a1 1a2 and 1b1 By Pahsmentioning

confidence: 98%

“…Both CYP1A1 and 1B1 were highly induced by the PAHs that are potent carcinogens in experimental animals Pelkonen & Nebert, 1982;Shimada et al, 2002Shimada et al, , 2003a. These PAHs include benzo[k]fluoranthene, benzo [b]fluoranthene, benzo [j]fluoranthene, benzo [a]pyrene, 3-methylcholanthrene, dibenz [a,h]anthracene, benz [a]anthracene and dibenzo [a,l]pyrene.…”

Section: (Viii) Induction Of Cyp1a1 1a2 and 1b1 By Pahsmentioning

confidence: 99%

Integrating Field Analyses with Laboratory Exposures to Assess Ecosystems Health

Hellou¹,

Beach²,

Leonard³

et al. 2012

Polycyclic Aromatic Compounds

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initiated a programme on the evaluation of the carcinogenic risk of chemicals to humans involving the production of critically evaluated monographs on individual chemicals. The programme was subsequently expanded to include evaluations of carcinogenic risks associated with exposures to complex mixtures, life-style factors and biological and physical agents, as well as those in specific occupations. The objective of the programme is to elaborate and publish in the form of monographs critical reviews of data on carcinogenicity for agents to which humans are known to be exposed and on specific exposure situations; to evaluate these data in terms of human risk with the help of international working groups of experts in chemical carcinogenesis Publications of the World Health Organization enjoy copyright protection in accordance with the provisions of Protocol 2 of the Universal Copyright Convention. All rights reserved.The International Agency for Research on Cancer welcomes requests for permission to reproduce or translate its publications, in part or in full. Requests for permission to reproduce or translate IARC publications -whether for sale or for noncommercial distribution -should be addressed to WHO Press, at the above address (fax: +41 22 791 4806; email: permissions@who.int).The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the World Health Organization concerning the legal status of any country, territory, city, or area or of its authorities, or concerning the delimitation of its frontiers or boundaries.The mention of specific companies or of certain manufacturers' products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters.The IARC Monographs Working Group alone is responsible for the views expressed in this publication. IARC Library Cataloguing in Publication Data NOTE TO THE READERThe term 'carcinogenic risk' in the IARC Monographs series is taken to mean that an agent is capable of causing cancer under some circumstances. The Monographs evaluate cancer hazards, despite the historical presence of the word 'risks' in the title.Inclusion of an agent in the Monographs does not imply that it is a carcinogen, only that the published data have been examined. Equally, the fact that an agent has not yet been evaluated in a Monograph does not mean that it is not carcinogenic.The evaluations of carcinogenic risk are made by international working groups of independent scientists and are qualitative in nature. No recommendation is given for regulation or legislation.Anyone who is aware of published data that may alter the evaluation of the carcinogenic risk of an agent to humans is encouraged to make this information available to the Section of IARC Monographs, International Agency for...

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Tissue-specific induction of cytochromes P450 1A1 and 1B1 by polycyclic aromatic hydrocarbons and polychlorinated biphenyls in engineered C57BL/6J mice of arylhydrocarbon receptor gene

Cited by 122 publications

References 39 publications

Effect of Lipopolysaccharide on the Xenobiotic-Induced Expression and Activity of Hepatic Cytochrome P450 in Mice

Effect of Lipopolysaccharide on the Xenobiotic-Induced Expression and Activity of Hepatic Cytochrome P450 in Mice

Diminished Carcinogen Detoxification Is a Novel Mechanism for Hypoxia-inducible Factor 1-mediated Genetic Instability

Integrating Field Analyses with Laboratory Exposures to Assess Ecosystems Health

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