2013 Fiscal Year Final Research Report
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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| 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 |
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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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