The DOI matches its Crossref record; 69 of the 70 references it cites were found in a registry or an index.
Role of Polymorphic Human Cytochrome P450 Enzymes in Estrone Oxidation
Abstract
Estrogen and its metabolites are believed to play important roles in breast cancer. The influence of genetic polymorphisms in the enzymes responsible for formation and disposition of estrogen on breast cancer risk may shed light on the importance of estrogen metabolites in this disease. However, for such studies to be valid, it is important to correctly identify the enzymes involved in estrogen bioactivation. Therefore, we assessed the human cytochrome P450-dependent oxidation of estrone using substrate concentrations that more closely approximate the maximum expected concentrations in breast tissue. The in vitro metabolism of estrone by recombinant human cytochrome P450 enzymes and human liver microsomes was studied. The formation of estrone metabolites (2-hydroxyestrone, 4-hydroxyestrone, and 16alpha-hydroxyestrone) was monitored by high-performance liquid chromatography. 2-Hydroxyestrone formation was catalyzed predominantly by CYP1A2, CYP1A1, and CYP1B1 enzymes; 4-hydroxyestrone formation was catalyzed predominantly by CYP1B1, CYP1A2, and CYP1A1 enzymes; and 16alpha-hydroxyestrone formation was catalyzed predominantly by CYP2C19, CYP1A1, and CYP3A5. This study confirms the important role of members of the CYP1 family in the 2-hydroxylation and 4-hydroxylation of estrone, but the enzymes identified as responsible for the 16alpha-hydroxylation of estrone are different from those previously identified. The relative importance of these enzymes in vivo would depend on the specific tissue expression of the enzymes. These enzymes are all known to be genetically variant in the human population, and additional studies to assess the role CYP1A2, CYP2C19, and CYP3A5 in breast cancer risk are indicated.
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“CYP3A4 is the major enzyme responsible for the 16α-hydroxylation of estrone in adults, though CYP1A1, CYP2C19 and CYP3A5 can also catalyze the reaction [315,316].”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [316]
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Cites
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“When the relative intrinsic clearances of the various enzymes were corrected for the differing expression levels in the typical human liver (51, 52), the predicted contribution from CYP1A2 was eight times higher than other CYP enzymes (Table 5).”
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Research works printed but not linked: 1
- Rodrigues AD. Integrated cytochrome P450 reaction phenotyping: attempting to bridge the gap between cDNA-expressed cytochromes P450 and native human liver microsomes. Biochem Pharmacol 1999;57:465–80.
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Nebert, D. W., & Dalton, T. P. (2006) · Nature reviews. Cancer · doi:10.1038/nrc2015 · Cited by 985
Schiffer, L., Barnard, L., Baranowski, E. S., Gilligan, L. C., Taylor, A. E., Arlt, W., Shackleton, C. H. L., & Storbeck, K.-H. (2019) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2019.105439 · Cited by 450
“CYP3A4 is the major enzyme responsible for the 16αhydroxylation of estrone in adults, though CYP1A1, CYP2C19 and CYP3A5 can also catalyze the reaction [315,316].”
Estrogen metabolism and breast cancer
Samavat, H., & Kurzer, M. S. (2014) · Cancer Letters · doi:10.1016/j.canlet.2014.04.018 · Cited by 401
Contributions of Human Enzymes in Carcinogen Metabolism
Rendić, S., & Guengerich, F. P. (2012) · Chemical Research in Toxicology · doi:10.1021/tx300132k · Cited by 281
Potential Mechanisms of Estrogen Quinone Carcinogenesis
Bolton, J. L., & Thatcher, G. R. J. (2007) · Chemical Research in Toxicology · doi:10.1021/tx700191p · Cited by 242
Metadata
- Authors
- Cribb, A. E., Knight, M. J., Dryer, D., Guernsey, J., Hender, K., Tesch, M., & Saleh, T. M.
- Affiliations
- University of Prince Edward Island (CA)
- 2Queen Elizabeth Hospital, Charlottetown, Prince Edward Island, Canada; and
- Dalhousie University (CA)
- Venue
- Cancer Epidemiology, Biomarkers & Prevention
- Published
- 2006-03-01
- Volume
- 15
- Issue
- 3
- Pages
- 551-558
- ISSN
- 1055-9965 (ISSN-L)
- 1538-7755
- OpenAlex
- W2141239229
- Cited by
- 118
- References
- 70
- Citations by year
- 2025: 3 · 2024: 5 · 2023: 8 · 2022: 7 · 2021: 6 · 2020: 3 · 2019: 6 · 2018: 3 · 2017: 4 · 2016: 2 · 2015: 5 · 2014: 8 · 2013: 7 · 2012: 8
- FWCI
- 7.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer Epidemiology Biomarkers & Prevention (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Catalyzed Oxygenation Mechanisms
- Keywords
- estrogen metabolism, cytochrome P450 polymorphisms, breast cancer risk, 2-hydroxyestrone, 4-hydroxyestrone, 16α-hydroxyestrone, CYP1A2, CYP1A1, CYP1B1, CYP2C19, CYP3A5, liver microsomes, genetic variation
- MeSH terms
- Breast Neoplasms, Chromatography, High Pressure Liquid, Cytochrome P-450 Enzyme System, Estrone, Female, Humans, Mixed Function Oxygenases, Hydroxylation, Microsomes, Liver, Oxidation-Reduction, Sensitivity and Specificity, Tumor Cells, Cultured, Biomarkers, Tumor, Cytochrome P-450 CYP1A1, Cytochrome P-450 CYP1A2, In Vitro Techniques
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