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Dramatic extension of tumor latency and correction of neurobehavioral phenotype in Atm-mutant mice with a nitroxide antioxidant
Gueven, N and Luff, J and Peng, C and Hosokawa, K and Bottle, SE and Lavin, MF, Dramatic extension of tumor latency and correction of neurobehavioral phenotype in Atm-mutant mice with a nitroxide antioxidant, Free Radical Biology and Medicine, 41, (6) pp. 992-1000. ISSN 0891-5849 (2006) [Refereed Article]
Copyright 2006 Elsevier Inc.
Mutations in the ATM gene (mutated in ataxia telangiectasia) in both humans and mice predispose to lymphoid tumors. A defect in this gene also causes neurodegeneration in humans and a less severe neurological phenotype in mice. There is some evidence that oxidative stress contributes to these defects, suggesting that antioxidants could alleviate the phenotype. We demonstrate here that the antioxidant 5-carboxy-1,1,3,3-tetramethylisoindolin-2-yloxyl (CTMIO) dramatically delays the onset of thymic lymphomas in Atm(-/-) mice which is not due to an enhancement of apoptosis by CTMIO. We also show that this compound corrects neurobehavioral deficits in these mice and reduces oxidative damage to Purkinje cells. The likely mechanism of action of CTMIO is due to a reduction in oxidative stress, which is protective against both the tumor progression and the development of neurological abnormalities. These data suggest that antioxidant therapy has considerable potential in the management of ataxia telangiectasia and possibly other neurodegenerative disorders where oxidative stress is implicated.
|Item Type:||Refereed Article|
|Keywords:||nitroxide antioxidants, cancer, drug discovery, ATM|
|Research Division:||Health Sciences|
|Research Group:||Health services and systems|
|Research Field:||Health services and systems not elsewhere classified|
|Objective Group:||Other health|
|Objective Field:||Other health not elsewhere classified|
|UTAS Author:||Gueven, N (Dr Nuri Guven)|
|Web of Science® Times Cited:||65|
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