This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Spencer, D. L. Articles by Walker, N. J. Search for Related Content PubMed PubMed Citation Articles by Spencer, D. L. Articles by Walker, N. J.

Quantitative Analysis of Constitutive and 2,3,7,8-Tetrachlorodibenzo-p-dioxin-induced Cytochrome P450 1B1 Expression in Human Lymphocytes¹

Laboratory of Computational Biology and Risk Analysis, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina 27709 [D. L. S., S. A. M., K. M. L., X. Y., J. A. G., C. R. M., G. W. L., N. J. W.], and Division of Toxicological Sciences, Johns Hopkins School of Hygiene and Public Health, Baltimore, Maryland 21205 [T. R. S.]

Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or dioxin) results in a broad spectrum of biological responses, including altered metabolism, disruption of normal hormone signaling pathways, reproductive and developmental effects, and cancer. Cytochrome P450 1B1 (CYP1B1) is a dioxin-inducible gene that is active in the formation of 4-hydroxyestradiol, a potentially genotoxic catechol estrogen. Therefore, the analysis of CYP1B1 in humans may be useful in establishing relationships between dioxin exposure and adverse health effects. In this study, we examined the expression of CYP1B1 in human peripheral blood lymphocytes of unexposed individuals using a quantitative reverse transcription-PCR method. Absolute CYP1B1 RNA levels varied more than 30-fold in uncultured mononuclear cells obtained from 10 individuals. In vitro treatment of mitogen-stimulated lymphocytes with TCDD for 1–5 days of culture resulted in a peak induction of CYP1B1 after 3 days. The induction of CYP1B1 RNA levels after 3 days of culture was dose-dependent, exhibited a maximum response above 10 nM TCDD, and varied greatly among different individuals. However, the half maximal dose required for this induction was similar between individuals and comparable to that observed in the MCF-7 and HepG2 human cell lines. These observations indicate that CYP1B1 exhibits variable constitutive expression and is inducible in vitro by TCDD in human lymphocytes and that the magnitude of induction varies within the population. These data define the suitability of CYP1B1 for use as a mechanistically based biomarker in ongoing molecular epidemiological studies of human populations exposed to dioxins and related chemicals that bind the aromatic hydrocarbon receptor.

This article has been cited by other articles:

				S. Zienolddiny, D. Campa, H. Lind, D. Ryberg, V. Skaug, L. B. Stangeland, F. Canzian, and A. Haugen A comprehensive analysis of phase I and phase II metabolism gene polymorphisms and risk of non-small cell lung cancer in smokers Carcinogenesis, June 1, 2008; 29(6): 1164 - 1169. [Abstract] [Full Text] [PDF]

				G. Siest, E. Jeannesson, J.-B. Marteau, A. Samara, B. Marie, M. Pfister, and S. Visvikis-Siest Transcription Factor and Drug-Metabolizing Enzyme Gene Expression in Lymphocytes from Healthy Human Subjects Drug Metab. Dispos., January 1, 2008; 36(1): 182 - 189. [Abstract] [Full Text] [PDF]

				R. H. Straub The Complex Role of Estrogens in Inflammation Endocr. Rev., August 1, 2007; 28(5): 521 - 574. [Abstract] [Full Text] [PDF]

				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]

				M. B. M. van Duursen, J. T. Sanderson, and M. van den Berg Cytochrome P450 1A1 and 1B1 in Human Blood Lymphocytes Are Not Suitable as Biomarkers of Exposure to Dioxin-like Compounds: Polymorphisms and Interindividual Variation in Expression and Inducibility Toxicol. Sci., May 1, 2005; 85(1): 703 - 712. [Abstract] [Full Text] [PDF]

				M. B.M. van Duursen, R. Fernandez Canton, T. Kocan, J. T. Sanderson, K. Kieviet, and M. van den Berg No Effect of CYP1B1 Val432Leu Polymorphism on CYP1B1 Messenger RNA Levels in an Organochlorine-Exposed Population in Slovakia Cancer Epidemiol. Biomarkers Prev., March 1, 2005; 14(3): 755 - 756. [Full Text] [PDF]

				S. Uno, T. P. Dalton, S. Derkenne, C. P. Curran, M. L. Miller, H. G. Shertzer, and D. W. Nebert Oral Exposure to Benzo[a]pyrene in the Mouse: Detoxication by Inducible Cytochrome P450 Is More Important Than Metabolic Activation Mol. Pharmacol., May 1, 2004; 65(5): 1225 - 1237. [Abstract] [Full Text]

				M. T. Landi, P. A. Bertazzi, A. Baccarelli, D. Consonni, S. Masten, G. Lucier, P. Mocarelli, L. Needham, N. Caporaso, and J. Grassman TCDD-mediated alterations in the AhR-dependent pathway in Seveso, Italy, 20 years after the accident Carcinogenesis, April 1, 2003; 24(4): 673 - 680. [Abstract] [Full Text] [PDF]

				K. Toide, H. Yamazaki, R. Nagashima, K. Itoh, S. Iwano, Y. Takahashi, S. Watanabe, and T. Kamataki Aryl Hydrocarbon Hydroxylase Represents CYP1B1, and not CYP1A1, in Human Freshly Isolated White Cells: Trimodal Distribution of Japanese Population According to Induction of CYP1B1 mRNA by Environmental Dioxins Cancer Epidemiol. Biomarkers Prev., March 1, 2003; 12(3): 219 - 222. [Abstract] [Full Text] [PDF]

				P. Lin, S.-W. Hu, and T.-H. Chang Correlation between Gene Expression of Aryl Hydrocarbon Receptor (AhR), Hydrocarbon Receptor Nuclear Translocator (Arnt), Cytochromes P4501A1 (CYP1A1) and 1B1 (CYP1B1), and Inducibility of CYP1A1 and CYP1B1 in Human Lymphocytes Toxicol. Sci., January 1, 2003; 71(1): 20 - 26. [Abstract] [Full Text] [PDF]

				J. M. Martinez, C. A. Afshari, P. R. Bushel, A. Masuda, T. Takahashi, and N. J. Walker Differential Toxicogenomic Responses to 2,3,7,8-Tetrachlorodibenzo-p-dioxin in Malignant and Nonmalignant Human Airway Epithelial Cells Toxicol. Sci., October 1, 2002; 69(2): 409 - 423. [Abstract] [Full Text] [PDF]

				D. P. Bofinger, L. Feng, L.-H. Chi, J. Love, F. D. Stephen, T. R. Sutter, K. G. Osteen, T. G. Costich, R. E. Batt, S. T. Koury, et al. Effect of TCDD Exposure on CYP1A1 and CYP1B1 Expression in Explant Cultures of Human Endometrium Toxicol. Sci., August 1, 2001; 62(2): 299 - 314. [Abstract] [Full Text] [PDF]

				C. Dassi, P. Brambilla, S. Signorini, P. Gerthoux, P. Molteni, R. Sala, and P. Mocarelli Quantification of Aromatic Hydrocarbon Receptor (AHR) and Related Genes by Calibrated Reverse Transcription-PCR in Blood Mononuclear Cells Clin. Chem., July 1, 2001; 47(7): 1311 - 1314. [Full Text] [PDF]

				T. S. Thurmond and T. A. Gasiewicz A Single Dose of 2,3,7,8-Tetrachlorodibenzo-p-dioxin Produces a Time- and Dose-Dependent Alteration in the Murine Bone Marrow B-Lymphocyte Maturation Profile Toxicol. Sci., November 1, 2000; 58(1): 88 - 95. [Abstract] [Full Text] [PDF]

				A. F. Badawi, E. L. Cavalieri, and E. G. Rogan Effect of chlorinated hydrocarbons on expression of cytochrome P450 1A1, 1A2 and 1B1 and 2- and 4-hydroxylation of 17{beta}-estradiol in female Sprague-Dawley rats Carcinogenesis, August 1, 2000; 21(8): 1593 - 1599. [Abstract] [Full Text] [PDF]

				B. C. Krovat, J. H. Tracy, and C. J. Omiecinski Fingerprinting of Cytochrome P450 and Microsomal Epoxide Hydrolase Gene Expression in Human Blood Cells Toxicol. Sci., June 1, 2000; 55(2): 352 - 360. [Abstract] [Full Text] [PDF]

				S. M. Heidel, K. Holston, J. T.M. Buters, F. J. Gonzalez, C. R. Jefcoate, and C. J. Czupyrynski Bone Marrow Stromal Cell Cytochrome P4501B1 Is Required for Pre-B Cell Apoptosis Induced by 7,12-Dimethylbenz[a]anthracene Mol. Pharmacol., December 1, 1999; 56(6): 1317 - 1323. [Abstract] [Full Text]