Skip Navigation

This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (99)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Kim, J. H.
Right arrow Articles by Sutter, T. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kim, J. H.
Right arrow Articles by Sutter, T. R.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Carcinogenesis, Vol 19, 1847-1853, Copyright © 1998 by Oxford University Press

ARTICLES

Metabolism of benzo[a]pyrene and benzo[a]pyrene-7,8-diol by human cytochrome P450 1B1

JH Kim, KH Stansbury, NJ Walker, MA Trush, PT Strickland and TR Sutter
Department of Environmental Health Sciences, The Johns Hopkins School of Hygiene and Public Health, Baltimore, MD 21205, USA.

Benzo[a]pyrene (B[a]P), a ubiquitous environmental, tobacco and dietary carcinogen, has been implicated in human cancer etiology. The role of human cytochrome P450 1B1 in the metabolism of B[a]P is poorly understood. Using microsomal preparations of human P450 1A1, 1A2 and 1B1 expressed in baculovirus-infected insect cells, as well as human and rat P450 1B1 expressed in yeast, we have determined the metabolism of B[a]P, with and without the addition of exogenous epoxide hydrolase, and B[a]P-7,8-dihydrodiol (7,8-diol), each substrate at a concentration of 10 microM. HPLC analysis detected eight major metabolites of B[a]P and four metabolites of the 7,8-diol. The results of these studies indicate that cytochrome P450 1B1 carries out metabolism of B[a]P along the pathway to the postulated ultimate carcinogen, the diol epoxide 2, at rates much higher than P450 1A2 but less than P450 1A1. The rates of formation of the 7,8-diol metabolite in incubations with epoxide hydrolase are 0.17 and 0.38 nmol/min/nmol P450 for human P450 1B1 and 1A1, respectively, and undetectable for 1A2. The rates of total tetrol metabolite formation from the 7,8-diol, which are indicative of diol epoxide formation, are 0.60, 0.43 and 2.58 nmol/min/nmol P450 for 1B1, 1A2 and 1A1 respectively. In agreement with other reports of rat P450 1B1 activity, our data show this rat enzyme to be very active for B[a]P and 7,8-diol, with rates higher than human P450 1B1. In addition to the established role of P450 1A1 in B[a]P metabolism, P450 1B1 may significantly contribute to B[a]P and 7,8-diol metabolism and carcinogenesis in rodent tumor models and in humans.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Mol. Pharmacol.Home page
P. H. Bui and O. Hankinson
Functional Characterization of Human Cytochrome P450 2S1 Using a Synthetic Gene-Expressed Protein in Escherichia coli
Mol. Pharmacol., November 1, 2009; 76(5): 1031 - 1043.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
P. H. Bui, E. L. Hsu, and O. Hankinson
Fatty Acid Hydroperoxides Support Cytochrome P450 2S1-Mediated Bioactivation of Benzo[a]pyrene-7,8-dihydrodiol
Mol. Pharmacol., November 1, 2009; 76(5): 1044 - 1052.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Prevention ResearchHome page
D. Hughes, J. B. Guttenplan, C. B. Marcus, K. Subbaramaiah, and A. J. Dannenberg
Heat Shock Protein 90 Inhibitors Suppress Aryl Hydrocarbon Receptor-Mediated Activation of CYP1A1 and CYP1B1 Transcription and DNA Adduct Formation
Cancer Prevention Research, November 1, 2008; 1(6): 485 - 493.
[Abstract] [Full Text] [PDF]

Home page
 Am J EpidemiolHome page
V. Paracchini, S. Raimondi, I. T. Gram, D. Kang, N. A. Kocabas, V. N. Kristensen, D. Li, F. F. Parl, T. Rylander-Rudqvist, P. Soucek, et al.
Meta- and Pooled Analyses of the Cytochrome P-450 1B1 Val432Leu Polymorphism and Breast Cancer: A HuGE-GSEC Review
Am. J. Epidemiol., January 15, 2007; 165(2): 115 - 125.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
L. Wang, B. E. Scheffler, and K. L. Willett
CYP1C1 Messenger RNA Expression is Inducible by Benzo[a]pyrene in Fundulus heteroclitus Embryos and Adults
Toxicol. Sci., October 1, 2006; 93(2): 331 - 340.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
P. A. Tsuji and T. Walle
Inhibition of benzo[a]pyrene-activating enzymes and DNA binding in human bronchial epithelial BEAS-2B cells by methoxylated flavonoids
Carcinogenesis, August 1, 2006; 27(8): 1579 - 1585.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
T. Walle, U. K. Walle, D. Sedmera, and M. Klausner
BENZO[A]PYRENE-INDUCED ORAL CARCINOGENESIS AND CHEMOPREVENTION: STUDIES IN BIOENGINEERED HUMAN TISSUE
Drug Metab. Dispos., March 1, 2006; 34(3): 346 - 350.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
H. Chang, L. W. Chang, Y.-H. Cheng, W.-T. Tsai, M.-X. Tsai, and P. Lin
Preferential Induction of CYP1A1 and CYP1B1 in CCSP-Positive Cells
Toxicol. Sci., January 1, 2006; 89(1): 205 - 213.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
E. Aklillu, S. Ovrebo, I. V. Botnen, C. Otter, and M. Ingelman-Sundberg
Characterization of Common CYP1B1 Variants with Different Capacity for Benzo[a]pyrene-7,8-Dihydrodiol Epoxide Formation from Benzo[a]pyrene
Cancer Res., June 15, 2005; 65(12): 5105 - 5111.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
S. S. De Buck, F. B. Bouche, A. Brandenburger, and C. P. Muller
Modulation of the metabolism and adverse effects of benzo[a]pyrene by a specific antibody: a novel host factor in environmental carcinogenesis?
Carcinogenesis, April 1, 2005; 26(4): 835 - 844.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Epidemiol. Biomarkers Prev.Home page
J. A. Doherty, N. S. Weiss, R. J. Freeman, D. A. Dightman, P. J. Thornton, J. R. Houck, L. F. Voigt, M. A. Rossing, S. M. Schwartz, and C. Chen
Genetic Factors in Catechol Estrogen Metabolism in Relation to the Risk of Endometrial Cancer
Cancer Epidemiol. Biomarkers Prev., February 1, 2005; 14(2): 357 - 366.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
J. L. Port, K. Yamaguchi, B. Du, M. De Lorenzo, M. Chang, P. M. Heerdt, L. Kopelovich, C. B. Marcus, N. K. Altorki, K. Subbaramaiah, et al.
Tobacco smoke induces CYP1B1 in the aerodigestive tract
Carcinogenesis, November 1, 2004; 25(11): 2275 - 2281.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
D. C. Spink, B. H. Katz, M. M. Hussain, B. T. Pentecost, Z. Cao, and B. C. Spink
Estrogen regulates Ah responsiveness in MCF-7 breast cancer cells
Carcinogenesis, December 1, 2003; 24(12): 1941 - 1950.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
J. S. Mammen, G. S. Pittman, Y. Li, F. Abou-Zahr, B. A. Bejjani, D. A. Bell, P. T. Strickland, and T. R. Sutter
Single amino acid mutations, but not common polymorphisms, decrease the activity of CYP1B1 against (-)benzo[a]pyrene-7R-trans-7,8-dihydrodiol
Carcinogenesis, July 1, 2003; 24(7): 1247 - 1255.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
M. Ramos-Gomez, P. M. Dolan, K. Itoh, M. Yamamoto, and T. W. Kensler
Interactive effects of nrf2 genotype and oltipraz on benzo[a]pyrene-DNA adducts and tumor yield in mice
Carcinogenesis, March 1, 2003; 24(3): 461 - 467.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
T. Shimada, K. Inoue, Y. Suzuki, T. Kawai, E. Azuma, T. Nakajima, M. Shindo, K. Kurose, A. Sugie, Y. Yamagishi, et al.
Arylhydrocarbon receptor-dependent induction of liver and lung cytochromes P450 1A1, 1A2, and 1B1 by polycyclic aromatic hydrocarbons and polychlorinated biphenyls in genetically engineered C57BL/6J mice
Carcinogenesis, July 1, 2002; 23(7): 1199 - 1207.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
D. C. Spink, B. H. Katz, M. M. Hussain, B. C. Spink, S. J. Wu, N. Liu, R. Pause, and L. S. Kaminsky
Induction of CYP1A1 and CYP1B1 in T-47D Human Breast Cancer Cells by Benzo[a]pyrene Is Diminished by Arsenite
Drug Metab. Dispos., March 1, 2002; 30(3): 262 - 269.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
S. A. Larsen-Su and D. E. Williams
Transplacental Exposure to Indole-3-carbinol Induces Sex-Specific Expression of CYP1A1 and CYP1B1 in the Liver of Fischer 344 Neonatal Rats
Toxicol. Sci., December 1, 2001; 64(2): 162 - 168.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
T. Shimada, Y. Oda, E. M. J. Gillam, F. P. Guengerich, and K. Inoue
Metabolic Activation of Polycyclic Aromatic Hydrocarbons and Other Procarcinogens by Cytochromes P450 1A1 and P450 1B1 Allelic Variants and Other Human Cytochromes P450 in Salmonella typhimurium NM2009
Drug Metab. Dispos., September 1, 2001; 29(9): 1176 - 1182.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
C. P. Marston, C. Pereira, J. Ferguson, K. Fischer, O. Hedstrom, W.-M. Dashwood, and W. M. Baird
Effect of a complex environmental mixture from coal tar containing polycyclic aromatic hydrocarbons (PAH) on the tumor initiation, PAH-DNA binding and metabolic activation of carcinogenic PAH in mouse epidermis
Carcinogenesis, July 1, 2001; 22(7): 1077 - 1086.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
J. Hukkanen, O. Pelkonen, and H. Raunio
Expression of xenobiotic-metabolizing enzymes in human pulmonary tissue: possible role in susceptibility for ILD
Eur. Respir. J., July 1, 2001; 18(32_suppl): 122S - 126s.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
S. D. Spivack, G. J. Hurteau, A. A. Reilly, K. M. Aldous, X. Ding, and L. S. Kaminsky
CYP1B1 Expression in Human Lung
Drug Metab. Dispos., June 1, 2001; 29(6): 916 - 922.
[Abstract] [Full Text]

Home page
 CarcinogenesisHome page
D. Schwarz, P. Kisselev, I. Cascorbi, W.-H. Schunck, and I. Roots
Differential metabolism of benzo[a]pyrene and benzo[a]pyrene-7,8-dihydrodiol by human CYP1A1 variants
Carcinogenesis, March 1, 2001; 22(3): 453 - 459.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
K. C. Fertuck, J. B. Matthews, and T. R. Zacharewski
Hydroxylated Benzo[a]pyrene Metabolites Are Responsible for in Vitro Estrogen Receptor-Mediated Gene Expression Induced by Benzo[a]pyrene, but Do Not Elicit Uterotrophic Effects in Vivo
Toxicol. Sci., February 1, 2001; 59(2): 231 - 240.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
K. R.K. Sticha, M. E. Staretz, M. Wang, H. Liang, P. M.J. Kenney, and S. S. Hecht
Effects of benzyl isothiocyanate and phenethyl isothiocyanate on benzo[a]pyrene metabolism and DNA adduct formation in the A/J mouse
Carcinogenesis, September 1, 2000; 21(9): 1711 - 1719.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
G. D. Charles, M. J. Bartels, T. R. Zacharewski, B. B. Gollapudi, N. L. Freshour, and E. W. Carney
Activity of Benzo[a]pyrene and Its Hydroxylated Metabolites in an Estrogen Receptor-{alpha} Reporter Gene Assay
Toxicol. Sci., June 1, 2000; 55(2): 320 - 326.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
A.-K. Alexandrie, M. Warholm, U. Carstensen, A. Axmon, L. Hagmar, J. O. Levin, C. Ostman, and A. Rannug
CYP1A1 and GSTM1 polymorphisms affect urinary 1-hydroxypyrene levels after PAH exposure
Carcinogenesis, April 1, 2000; 21(4): 669 - 676.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
Y. Morel, N. Mermod, and R. Barouki
An Autoregulatory Loop Controlling CYP1A1 Gene Expression: Role of H2O2 and NFI
Mol. Cell. Biol., October 1, 1999; 19(10): 6825 - 6832.
[Abstract] [Full Text] [PDF]

Home page
 JNCI J Natl Cancer InstHome page
S. S. Hecht
Tobacco Smoke Carcinogens and Lung Cancer
J Natl Cancer Inst, July 21, 1999; 91(14): 1194 - 1210.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.