Complete cDNA sequence of a human dioxin-inducible mRNA identifies a new gene subfamily of cytochrome P450 that maps to chromosome 2.

Sutter, Thomas R.; Tang, Yong Ming; Hayes, Carrie L.; Wo, Yu Yuan P.; Jabs, Ethylin Wang; Li, Xiang; Yin, Hong; Cody, Chris W.; Greenlee, William F.

doi:10.1016/s0021-9258(17)36803-5

Cited by 425 publications

(65 citation statements)

References 44 publications

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“…CYP1B1 can efficiently metabolize 7,12-dimethylbenz[a]anthracene (57), a highly potent polycyclic aromatic hydrocarbon carcinogen. In contrast to CYP 1 A 1, CYP 1 B is constitutively expressed in several tissues, including breast, adrenal gland, prostate, testes, and ovary (4,7,73). The expression pattern and catalytic activity of CYP1B1 is similar in mice and humans.…”

Section: Cyp1b1 Knock-out (Cyp1b1-/-) Micementioning

confidence: 99%

Using Cytochrome P-450 Gene Knock-Out Mice to Study Chemical Metabolism, Toxicity, and Carcinogenicity

2000

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Cytochrome P-450 (CYP) enzymes are heme-containing proteins that carry out oxidative metabolism of a wide range of structurally diverse exogenous chemicals and therapeutic agents as well as endogenous compounds. For some of these xenobiotics, oxidative metabolism results in the formation of toxic, mutagenic, or carcinogenic metabolites. In the past, the role of CYP enzymes in metabolism and chemical-induced toxicity was studied indirectly through use of specific antibodies or inducers and inhibitors of these enzymes. Progress in molecular biology and the ability to bioengineer animal models that do not express CYP1A2, CYP1A1, CYP1B1, CYP2E1, or both CYP1A2 and CYP2E1 isozymes has allowed for direct investigations of the in vivo role of these enzymes in the metabolism, toxicity, and carcinogenicity of xenobiotics. This article reviews research conducted to date that utilizes these genetically bioengineered mice in metabolism, toxicity, or carcinogenicity studies of chemicals. Some studies showed a positive correlation between in vivo results and in vitro predictions for the role of a specific CYP in chemical-induced effects, whereas other studies did not support in vitro predictions. Work reviewed herein demonstrates the importance of using animal models for investigating the role of specific CYP enzymes in metabolism and chemical-induced toxicity or carcinogenicity rather than relying solely on in vitro techniques. Eventually, studies of this nature will facilitate a more accurate assessment of human risks with regard to chemicals by helping us to understand the relationships between chemical metabolism, carcinogenicity, and polymorphisms in CYP enzymes.

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Section: Cyp1b1 Knock-out (Cyp1b1-/-) Micementioning

confidence: 99%

Using Cytochrome P-450 Gene Knock-Out Mice to Study Chemical Metabolism, Toxicity, and Carcinogenicity

2000

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“…12,15,16,21 CYP1B1 and other genes of the CYP450 family catalyze NADPH-supported monooxygenation of diverse xenobiotics and endogenous molecules. 13,18 Strong expression of CYP1B1 in the fetal human and murine eye indicates that CYP1B1 plays an important role in ocular development and function. 3,6,17 Recently, our group demonstrated that Cyp1b1 deficiency significantly impaired trabecular cell function and oxidative homeostasis of the TM tissue in mice.…”

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confidence: 99%

Ultrastructural Abnormalities of the Trabecular Meshwork Extracellular Matrix in Cyp1b1-Deficient Mice

et al. 2014

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Cytochrome P450 1B1 (CYP1B1) is highly expressed in human and murine ocular tissues during development. Mutations in this gene are implicated in the development of primary congenital glaucoma (PCG) in humans. Mice deficient in Cyp1b1 (Cyp1b1−/−) present developmental abnormalities similar to human primary congenital glaucoma. The present work describes the ultrastructural morphology of the iridocorneal angle of 42 eyes from 1 week to 8-month-old Cyp1b1−/− mice. Morphometric and semiquantitative analysis of the data revealed that 3-week-old Cyp1b1−/− mice present significantly (p = 0.002) decreased amount of trabecular meshwork (TM) collagen and higher TM endothelial cell and collagen lesion scores (p = 0.002) than age-matched controls. Collagen loss and lesion scores were progressively increased in older animals with 8-month old animals presenting severe atrophy of the TM. Our findings advance the understanding of the effects of CYP1B1 mutations in the TM development and primary congenital glaucoma, and suggest a link between TM morphologic alterations and increased intraocular pressure.

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“…C ytochrome P450 (P450) CYP1B1 is the only known member of a recently identified subfamily of the CYP1 gene family. Human CYP1B1 was originally isolated from a dioxin-treated keratinocyte cell line (Sutter et al 1994) as part of a series of investigations to identify differential expression of genes caused by exposure to dioxin. The human CYP1B1 gene is located on chromosome 2p22-21 spanning 12 kb and is composed of three exons and two introns (Tang et al 1996).…”

mentioning

confidence: 99%

“…The human CYP1B1 gene is located on chromosome 2p22-21 spanning 12 kb and is composed of three exons and two introns (Tang et al 1996). The mRNA is 5.2 kb and encodes for a protein of 543 amino acids (Sutter et al 1994). This is the largest known human P450 gene, in terms of both mRNA size and number of amino acids, and is also the simplest structurally.…”

mentioning

confidence: 99%

Immunohistochemical Localization of Cytochrome P450 CYP1B1 in Breast Cancer with Monoclonal Antibodies Specific for CYP1B1

McFadyen

Breeman

Payne

et al. 1999

J Histochem Cytochem.

105

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SUMMARY Cytochrome P450 CYP1B1 is a recently identified member of the CYP1 P450 family. We have shown that this P450 displays increased expression in several types of human cancer, indicating that CYP1B1 is a potential tumor biomarker. In this study we developed monoclonal antibodies (MAbs) to CYP1B1 that are effective on formalin-fixed, paraffin-embedded tissue sections and investigated the presence of CYP1B1 in a series of primary breast cancers. The MAbs were generated using a synthetic peptide coupled to carrier protein as the immunogen. The MAbs specifically recognized CYP1B1 and did not recognize either CYP1A1 or CYP1A2, related CYP1 forms. The MAbs were tested by immunohistochemistry and were found to be effective on formalin-fixed, paraffin-embedded tissue sections. The majority of breast cancers showed positive immunoreactivity for CYP1B1, and in each case CYP1B1 was specifically localized to tumor cells. The presence of CYP1B1 in breast cancer cells is likely to contribute to their metabolism of estradiol because CYP1B1 is a specific estradiol hydroxylase.

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Complete cDNA sequence of a human dioxin-inducible mRNA identifies a new gene subfamily of cytochrome P450 that maps to chromosome 2.

Cited by 425 publications

References 44 publications

Using Cytochrome P-450 Gene Knock-Out Mice to Study Chemical Metabolism, Toxicity, and Carcinogenicity

Using Cytochrome P-450 Gene Knock-Out Mice to Study Chemical Metabolism, Toxicity, and Carcinogenicity

Ultrastructural Abnormalities of the Trabecular Meshwork Extracellular Matrix in Cyp1b1-Deficient Mice

Immunohistochemical Localization of Cytochrome P450 CYP1B1 in Breast Cancer with Monoclonal Antibodies Specific for CYP1B1

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