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Dramatic extension of tumor latency and correction of neurobehavioral phenotype in Atm-mutant mice with a nitroxide antioxidant

Citation

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 Statement

Copyright 2006 Elsevier Inc.

DOI: doi:10.1016/j.freeradbiomed.2006.06.018

Abstract

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 Details

Item Type:Refereed Article
Keywords:nitroxide antioxidants, cancer, drug discovery, ATM
Research Division:Medical and Health Sciences
Research Group:Other Medical and Health Sciences
Research Field:Medical and Health Sciences not elsewhere classified
Objective Division:Health
Objective Group:Other Health
Objective Field:Health not elsewhere classified
Author:Gueven, N (Dr Nuri Guven)
ID Code:79282
Year Published:2006
Web of Science® Times Cited:44
Deposited By:Pharmacy
Deposited On:2012-08-29
Last Modified:2014-11-05
Downloads:0

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