University Of Tasmania

File(s) under permanent embargo

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

journal contribution
posted on 2023-05-17, 13:02 authored by Nuri GuvenNuri Guven, Luff, J, Peng, C, Hosokawa, K, Bottle, SE, Lavin, MF
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.


Publication title

Free Radical Biology and Medicine










School of Pharmacy and Pharmacology


Pergamon-Elsevier Science Ltd

Place of publication

The Boulevard, Langford Lane, Kidlington, Oxford, England, Ox5 1Gb

Rights statement

Copyright 2006 Elsevier Inc.

Repository Status

  • Restricted

Socio-economic Objectives

Other health not elsewhere classified

Usage metrics

    University Of Tasmania