Mechanism analysis of progressive neurological abnormalities in xeroderma pigmentosum group A patients
Project/Area Number |
26550042
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Multi-year Fund |
Research Field |
Risk sciences of radiation and chemicals
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Research Institution | Nara Medical University |
Principal Investigator |
Mori Toshio 奈良県立医科大学, 医学部, 研究教授 (10115280)
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Research Collaborator |
Brooks P. J.
Nakane Hironobu
Hayashi Masaharu
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Project Period (FY) |
2014-04-01 – 2017-03-31
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Project Status |
Completed (Fiscal Year 2016)
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Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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Keywords | 色素性乾皮症 / 神経障害 / 酸化的DNA損傷 / サイクロプリン / モノクローナル抗体 / DNA修復異常 / 活性酸素 / ヌクレオチド除去修復 / 酵素標識免疫法 |
Outline of Final Research Achievements |
Xeroderma pigmentosum group A (XP-A) patients develop progressive neurological abnormalities, which has been hypothesized to be associated with a type of oxidatively generated DNA damage called purine 8,5’-cyclo-2’-deoxynucleosides. Thus, we generated a monoclonal antibody specific for 8,5’-cyclo-2’-deoxynadenosine (Cyclo-dA) in DNA. The immunoassay revealed a linear dose-response between known amounts of Cyclo-dA in oligonucleotides and the antibody binding to them with a detection sensitivity of about 1 lesion/10<6> bases in a 1 ug DNA sample. We compared the amounts of Cyclo-dA accumulated in organs between wild type and XP-A mice with ages from 5 months to 29 months. We found that XP-A mice accumulate significantly higher amounts of Cyclo-dA in brains than do wild type mice, supporting the hypothesis.
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Report
(4 results)
Research Products
(17 results)
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[Journal Article] Radiation-induced RhoGDIβ cleavage leads to perturbation of cell polarity: a possible link to cancer spreading2016
Author(s)
Fujiwara, M., Okamoto, M., Hori, M., Suga, H., Jikihara, H., Sugihara, Y., Shimamoto, F., Mori, T., Nakaoji, K., Hamada, K., Ota, T., Wiedemuth, R., Temme, A., and Tatsuka, M.
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Journal Title
J Cell Physiol
Volume: 0
Issue: 11
Pages: 0-0
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Functional regulation of the DNA damage-recognition factor DDB2 by ubiquitination and interaction with xeroderma pigmentosum group C protein.2015
Author(s)
Syota Matsumoto, Eric S. Fischer, Takeshi Yasuda, Naoshi Dohmae, Shigenori Iwai, Toshio Mori, Ryotaro Nishi, Ken-ichi Yoshino, Wataru Sakai, Fumio Hanaoka, Nicolas H. Thoma, Kaoru Sugasawa
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Journal Title
Nucleic Acids Research
Volume: 3
Issue: 3
Pages: 1700-1713
DOI
Related Report
Peer Reviewed / Open Access
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