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Exposure to benzo[a]pyrene of hepatic cytochrome P450 reductase null (HRN) and P450 reductase conditional null (RCN) mice

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Exposure to benzo[a]pyrene of hepatic cytochrome P450 reductase null (HRN) and P450 reductase conditional null (RCN) mice : detection of benzo[a]pyrene diol epoxide-DNA adducts by immunohistochemistry and P-postlabelling. / Arlt, Volker M.; Poirier, Miriam C.; Sykes, Sarah E.; John, Kaarthik; Moserova, Michaela; Stiborova, Marie; Wolf, C. Roland; Henderson, Colin J.; Phillips, David H.

In: Toxicology Letters, Vol. 213, No. 2, 2012, p. 160-166.

Research output: Contribution to journalArticle

Harvard

Arlt, VM, Poirier, MC, Sykes, SE, John, K, Moserova, M, Stiborova, M, Wolf, CR, Henderson, CJ & Phillips, DH 2012, 'Exposure to benzo[a]pyrene of hepatic cytochrome P450 reductase null (HRN) and P450 reductase conditional null (RCN) mice: detection of benzo[a]pyrene diol epoxide-DNA adducts by immunohistochemistry and P-postlabelling' Toxicology Letters, vol 213, no. 2, pp. 160-166., 10.1016/j.toxlet.2012.06.016

APA

Arlt, V. M., Poirier, M. C., Sykes, S. E., John, K., Moserova, M., Stiborova, M., ... Phillips, D. H. (2012). Exposure to benzo[a]pyrene of hepatic cytochrome P450 reductase null (HRN) and P450 reductase conditional null (RCN) mice: detection of benzo[a]pyrene diol epoxide-DNA adducts by immunohistochemistry and P-postlabelling. Toxicology Letters, 213(2), 160-166. 10.1016/j.toxlet.2012.06.016

Vancouver

Arlt VM, Poirier MC, Sykes SE, John K, Moserova M, Stiborova M et al. Exposure to benzo[a]pyrene of hepatic cytochrome P450 reductase null (HRN) and P450 reductase conditional null (RCN) mice: detection of benzo[a]pyrene diol epoxide-DNA adducts by immunohistochemistry and P-postlabelling. Toxicology Letters. 2012;213(2):160-166. Available from: 10.1016/j.toxlet.2012.06.016

Author

Arlt, Volker M.; Poirier, Miriam C.; Sykes, Sarah E.; John, Kaarthik; Moserova, Michaela; Stiborova, Marie; Wolf, C. Roland; Henderson, Colin J.; Phillips, David H. / Exposure to benzo[a]pyrene of hepatic cytochrome P450 reductase null (HRN) and P450 reductase conditional null (RCN) mice : detection of benzo[a]pyrene diol epoxide-DNA adducts by immunohistochemistry and P-postlabelling.

In: Toxicology Letters, Vol. 213, No. 2, 2012, p. 160-166.

Research output: Contribution to journalArticle

Bibtex - Download

@article{a051bb07c77744d48270028ab28a03e6,
title = "Exposure to benzo[a]pyrene of hepatic cytochrome P450 reductase null (HRN) and P450 reductase conditional null (RCN) mice: detection of benzo[a]pyrene diol epoxide-DNA adducts by immunohistochemistry and P-postlabelling",
keywords = "Animals, Benzo(a)pyrene, Cytochrome P-450 CYP1A1, Cytochromes b5, DNA Adducts, DNA Damage, Female, Hepatocytes, Immunohistochemistry, Liver, Mice, Mice, Inbred C57BL, Mice, Knockout, Microsomes, Liver, NADPH-Ferrihemoprotein Reductase",
author = "Arlt, {Volker M.} and Poirier, {Miriam C.} and Sykes, {Sarah E.} and Kaarthik John and Michaela Moserova and Marie Stiborova and Wolf, {C. Roland} and Henderson, {Colin J.} and Phillips, {David H.}",
note = "Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.",
year = "2012",
doi = "10.1016/j.toxlet.2012.06.016",
volume = "213",
number = "2",
pages = "160--166",
journal = "Toxicology Letters",
issn = "0378-4274",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Exposure to benzo[a]pyrene of hepatic cytochrome P450 reductase null (HRN) and P450 reductase conditional null (RCN) mice

T2 - detection of benzo[a]pyrene diol epoxide-DNA adducts by immunohistochemistry and P-postlabelling

A1 - Arlt,Volker M.

A1 - Poirier,Miriam C.

A1 - Sykes,Sarah E.

A1 - John,Kaarthik

A1 - Moserova,Michaela

A1 - Stiborova,Marie

A1 - Wolf,C. Roland

A1 - Henderson,Colin J.

A1 - Phillips,David H.

AU - Arlt,Volker M.

AU - Poirier,Miriam C.

AU - Sykes,Sarah E.

AU - John,Kaarthik

AU - Moserova,Michaela

AU - Stiborova,Marie

AU - Wolf,C. Roland

AU - Henderson,Colin J.

AU - Phillips,David H.

PY - 2012

Y1 - 2012

N2 - Benzo[a]pyrene (BaP) is a widespread environmental carcinogen activated by cytochrome P450 (P450) enzymes. In Hepatic P450 Reductase Null (HRN) and Reductase Conditional Null (RCN) mice, P450 oxidoreductase (Por) is deleted specifically in hepatocytes, resulting in the loss of essentially all hepatic P450 function. Treatment of HRN mice with a single i.p. or oral dose of BaP (12.5 or 125mg/kgbody weight) resulted in higher DNA adduct levels in liver (up to 10-fold) than in wild-type (WT) mice, indicating that hepatic P450s appear to be more important for BaP detoxification in vivo. Similar results were obtained in RCN mice. We tested whether differences between hepatocytes and non-hepatocytes in P450 activity may underlie the increased liver BaP-DNA binding in HRN mice. Cellular localisation by immunohistochemistry of BaP-DNA adducts showed that HRN mice have ample capacity for formation of BaP-DNA adducts in liver, indicating that the metabolic process does not result in the generation of a reactive species different from that formed in WT mice. However, increased protein expression of cytochrome b in hepatic microsomes of HRN relative to WT mice suggests that cytochrome b may modulate the P450-mediated bioactivation of BaP in HRN mice, partially substituting the function of Por. © 2012 Elsevier Ireland Ltd.

AB - Benzo[a]pyrene (BaP) is a widespread environmental carcinogen activated by cytochrome P450 (P450) enzymes. In Hepatic P450 Reductase Null (HRN) and Reductase Conditional Null (RCN) mice, P450 oxidoreductase (Por) is deleted specifically in hepatocytes, resulting in the loss of essentially all hepatic P450 function. Treatment of HRN mice with a single i.p. or oral dose of BaP (12.5 or 125mg/kgbody weight) resulted in higher DNA adduct levels in liver (up to 10-fold) than in wild-type (WT) mice, indicating that hepatic P450s appear to be more important for BaP detoxification in vivo. Similar results were obtained in RCN mice. We tested whether differences between hepatocytes and non-hepatocytes in P450 activity may underlie the increased liver BaP-DNA binding in HRN mice. Cellular localisation by immunohistochemistry of BaP-DNA adducts showed that HRN mice have ample capacity for formation of BaP-DNA adducts in liver, indicating that the metabolic process does not result in the generation of a reactive species different from that formed in WT mice. However, increased protein expression of cytochrome b in hepatic microsomes of HRN relative to WT mice suggests that cytochrome b may modulate the P450-mediated bioactivation of BaP in HRN mice, partially substituting the function of Por. © 2012 Elsevier Ireland Ltd.

KW - Animals

KW - Benzo(a)pyrene

KW - Cytochrome P-450 CYP1A1

KW - Cytochromes b5

KW - DNA Adducts

KW - DNA Damage

KW - Female

KW - Hepatocytes

KW - Immunohistochemistry

KW - Liver

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Microsomes, Liver

KW - NADPH-Ferrihemoprotein Reductase

UR - http://www.scopus.com/inward/record.url?scp=84864487999&partnerID=8YFLogxK

U2 - 10.1016/j.toxlet.2012.06.016

DO - 10.1016/j.toxlet.2012.06.016

M1 - Article

JO - Toxicology Letters

JF - Toxicology Letters

SN - 0378-4274

IS - 2

VL - 213

SP - 160

EP - 166

ER -

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