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

Gueven, Nuri, Luff, John, Peng, Cheng, Hosokawa, Kazuyuki, Bottle, Steven E. and Lavin, Martin F. (2006) 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: 992-1000. doi:10.1016/j.freeradbiomed.2006.06.018


Author Gueven, Nuri
Luff, John
Peng, Cheng
Hosokawa, Kazuyuki
Bottle, Steven E.
Lavin, Martin F.
Title Dramatic extension of tumor latency and correction of neurobehavioral phenotype in Atm-mutant mice with a nitroxide antioxidant
Journal name Free Radical Biology and Medicine   Check publisher's open access policy
ISSN 0891-5849
Publication date 2006-09-15
Sub-type Article (original research)
DOI 10.1016/j.freeradbiomed.2006.06.018
Open Access Status Not Open Access
Volume 41
Issue 6
Start page 992
End page 1000
Total pages 9
Editor K. J. A. Davies
W. A. Pryor
Place of publication New York, NY, United States
Publisher Elsevier
Collection year 2006
Language eng
Subject C1
320304 Medical Biochemistry - Nucleic Acids
730108 Cancer and related disorders
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. (c) 2006 Elsevier Inc. All rights reserved.
Keyword Endocrinology & Metabolism
Ataxia Telangiectasia
Nitroxide
Oxidative Stress
Neurodegeneration
Leukemia
Lymphoma
Ataxia-telangiectasia Gene
Increased Oxidative Stress
Deficient Mice
Superoxide-dismutase
Dna-damage
Defects
Cells
Lymphoma
Weight
Growth
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
2007 Higher Education Research Data Collection
School of Medicine Publications
 
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Created: Wed, 15 Aug 2007, 10:07:32 EST