Induction and repair of 4-OHEN-DNA adducts in human breast cancer cells by the metabolites of equine estrogens
| Project/Area Number |
23510081
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Risk sciences of radiation/Chemicals
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| Research Institution | Nara Medical University |
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Principal Investigator |
MORI Toshio 奈良県立医科大学, 医学部, 研究教授 (10115280)
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| Co-Investigator(Kenkyū-buntansha) |
IWAMOTO Takaaki 奈良県立医科大学, 医学部, 博士研究員 (20448773)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 人体有害物質 / エストロゲン補充療法 / 乳がん / 4-OHEN-DNA付加体 / 有害化学物質 / ヌクレオチド除去修復 / DNA付加体 |
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| Research Abstract |
Hormone replacement therapy (HRT) is widely used to decrease menopausal symptoms in post-menopausal women. However, long-term HRT increases the incidence of breast, ovarian and endometrial cancers. 4-Hydroxyequilenin (4-OHEN), a metabolite of equine estrogens present in common HRT formulations (Premarin), is capable of producing bulky 4-OHEN-DNA adducts. An immunological assay using our adduct-specific antibodies revealed that 4-OHEN-DNA adducts are repaired inefficiently in human breast cancer cells. MTS assay revealed that similar 4-OHEN sensitivities are observed between human normal and repair-deficient cells. Moreover, histones including human H1 competitively inhibited the binding of the antibodies to 4-OHEN-DNA adducts in a concentration-dependent manner, which are considered as a model of damage-recognising repair protein. Thus, the formation of DNA adducts with inefficient repair character might be involved in carcinogenesis process of Premarin-induced cancers.
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Report
(4 results)
Research Products
(22 results)
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[Journal Article] Characterization of three XPG-defective patients identifies three missense mutations that impair repair and transcription2013
Author(s)
A. Schafer, S. Schubert, A. Gratchev, C. Seebode, A. Apel, P. Laspe, L. Hofmann, A. Ohlenbusch, T. Mori, N. Kobayashi, A. Schurer, M. P. Schon, S. Emmert
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Journal Title
J. Invest. Dermatol
Volume: 133
Pages: 1841-1849
Related Report
Peer Reviewed
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[Journal Article] Characterization of three XPG-defective patients identifies three missense mutations that impair repair and transcription.2013
Author(s)
A. Schafer, S. Schubert, A. Gratchev, C. Seebode, A. Apel, P. Laspe, L. Hofmann, A. Ohlenbusch, T. Mori, N. Kobayashi, A. Schurer, M.P. Schon, S. Emmert.
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Journal Title
J. Invest. Dermatol.
Volume: 133
Issue: 7
Pages: 1841-1849
DOI
Related Report
Peer Reviewed
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[Journal Article] Tmem100, an ALK1 signaling-dependent gene essential for arterial endothelium differentiation and vascular morphogenesis2012
Author(s)
S. Somekawa, K. Imagawa, H. Hayashi, M. Sakabe, T. Ioka, G .E. Sato, K. Inada, T. Iwamoto, T. Mori, S. Uemura, O. Nakagawa, and Y. Saito
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Journal Title
Proc. Natl. Acad. Sci. USA
Volume: 109
Pages: 12064-12069
Related Report
Peer Reviewed
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[Journal Article] NBS1 recruits RAD18 via a RAD6-like domain and regulates pol-eta-dependent translesion DNA synthesis2011
Author(s)
H. Yanagihara, J. Kobayashi, S. Tateishi, A. Kato, S. Matsuura, H. Tauchi, K. Yamada, J. Takezawa, K. Sugasawa, C. Masutani, F. Hanaoka, C. M. Weemaes, T. Mori, L. Zou, and K. Komatsu
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Journal Title
Mol. Cell
Volume: 43
Pages: 788-797
Related Report
Peer Reviewed
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