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- Publisher Website: 10.4049/jimmunol.178.1.103
- Scopus: eid_2-s2.0-33845969499
- PMID: 17182545
- WOS: WOS:000243120900012
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Article: Regulation of reactive oxygen species by Atm is essential for proper response to DNA double-strand breaks in lymphocytes
Title | Regulation of reactive oxygen species by Atm is essential for proper response to DNA double-strand breaks in lymphocytes |
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Authors | |
Issue Date | 2007 |
Citation | Journal of Immunology, 2007, v. 178, n. 1, p. 103-110 How to Cite? |
Abstract | The ataxia telangiectasia-mutated (ATM) gene plays a pivotal role in the maintenance of genomic stability. Although it has been recently shown that antioxidative agents inhibited lymphomagenesis in Atm-/- mice, the mechanisms remain unclear. In this study, we intensively investigated the roles of reactive oxygen species (ROS) in phenotypes of Atm-/- mice. Reduction of ROS by the antioxidant N-acetyl-L-cysteine (NAC) prevented the emergence of senescent phenotypes in Atm-/- moose embryonic fibroblasts, hypersensitivity to total body irradiation, and thymic lymphomagenesis in Atm-/- mice. To understand the mechanisms for prevention of lymphomagenesis, we analyzed development of pretumor lymphocytes in Atm-/- mice. Impairment of Ig class switch recombination seen in Atm-/- mice was mitigated by NAC, indicating that ROS elevation leads to abnormal response to programmed double-strand breaks in vivo. Significantly, in vivo administration of NAC to Atm-/- mice restored normal T cell development and inhibited aberrant V(D)J recombination. We conclude that Atm-mediated ROS regulation is essential for proper DNA recombination, preventing immunodeficiency, and lymphomagenesis. Copyright © 2006 by The American Association of Immunologists, Inc. |
Persistent Identifier | http://hdl.handle.net/10722/291777 |
ISSN | 2021 Impact Factor: 5.426 2020 SCImago Journal Rankings: 2.737 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Ito, Keisuke | - |
dc.contributor.author | Takubo, Keiyo | - |
dc.contributor.author | Arai, Fumio | - |
dc.contributor.author | Satoh, Hitoshi | - |
dc.contributor.author | Matsuoka, Sahoko | - |
dc.contributor.author | Ohmura, Masako | - |
dc.contributor.author | Naka, Kazuhito | - |
dc.contributor.author | Azuma, Masaki | - |
dc.contributor.author | Miyamoto, Kana | - |
dc.contributor.author | Hosokawa, Kentaro | - |
dc.contributor.author | Ikeda, Yasuo | - |
dc.contributor.author | Mak, Tak W. | - |
dc.contributor.author | Suda, Toshio | - |
dc.contributor.author | Hirao, Atsushi | - |
dc.date.accessioned | 2020-11-17T14:55:05Z | - |
dc.date.available | 2020-11-17T14:55:05Z | - |
dc.date.issued | 2007 | - |
dc.identifier.citation | Journal of Immunology, 2007, v. 178, n. 1, p. 103-110 | - |
dc.identifier.issn | 0022-1767 | - |
dc.identifier.uri | http://hdl.handle.net/10722/291777 | - |
dc.description.abstract | The ataxia telangiectasia-mutated (ATM) gene plays a pivotal role in the maintenance of genomic stability. Although it has been recently shown that antioxidative agents inhibited lymphomagenesis in Atm-/- mice, the mechanisms remain unclear. In this study, we intensively investigated the roles of reactive oxygen species (ROS) in phenotypes of Atm-/- mice. Reduction of ROS by the antioxidant N-acetyl-L-cysteine (NAC) prevented the emergence of senescent phenotypes in Atm-/- moose embryonic fibroblasts, hypersensitivity to total body irradiation, and thymic lymphomagenesis in Atm-/- mice. To understand the mechanisms for prevention of lymphomagenesis, we analyzed development of pretumor lymphocytes in Atm-/- mice. Impairment of Ig class switch recombination seen in Atm-/- mice was mitigated by NAC, indicating that ROS elevation leads to abnormal response to programmed double-strand breaks in vivo. Significantly, in vivo administration of NAC to Atm-/- mice restored normal T cell development and inhibited aberrant V(D)J recombination. We conclude that Atm-mediated ROS regulation is essential for proper DNA recombination, preventing immunodeficiency, and lymphomagenesis. Copyright © 2006 by The American Association of Immunologists, Inc. | - |
dc.language | eng | - |
dc.relation.ispartof | Journal of Immunology | - |
dc.title | Regulation of reactive oxygen species by Atm is essential for proper response to DNA double-strand breaks in lymphocytes | - |
dc.type | Article | - |
dc.description.nature | link_to_OA_fulltext | - |
dc.identifier.doi | 10.4049/jimmunol.178.1.103 | - |
dc.identifier.pmid | 17182545 | - |
dc.identifier.scopus | eid_2-s2.0-33845969499 | - |
dc.identifier.volume | 178 | - |
dc.identifier.issue | 1 | - |
dc.identifier.spage | 103 | - |
dc.identifier.epage | 110 | - |
dc.identifier.isi | WOS:000243120900012 | - |
dc.identifier.f1000 | 1060954 | - |
dc.identifier.issnl | 0022-1767 | - |