Other
14 Authors
- Satoh H,
- Ito K,
- Hosokawa K,
- Naka K,
- Arai F,
- Ohmura M,
- Matsuoka S,
- Takubo K,
- Hirao A,
- Mak TW,
- Miyamoto K,
- Ikeda Y,
- Suda T,
- Azuma M
| First Author | Ito K | Year | 2007 |
| Journal | J Immunol | Volume | 178 |
| Issue | 1 | Pages | 103-10 |
| PubMed ID | 17182545 | Mgi Jnum | J:120272 |
| Mgi Id | MGI:3706201 | Doi | 10.4049/jimmunol.178.1.103 |
| Citation | Ito K, et al. (2007) Regulation of reactive oxygen species by Atm is essential for proper response to DNA double-strand breaks in lymphocytes. J Immunol 178(1):103-10 |
| abstractText | 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(-/-) mouse 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. |
