期刊
FOOD AND CHEMICAL TOXICOLOGY
卷 46, 期 4, 页码 1371-1377出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.fct.2007.08.028
关键词
Atm; mouse; antioxidants; chemoprevention; lymphoma; neuromotor performance
资金
- NIEHS NIH HHS [U54 ES012078, U54ES12078, R01 ES09519, R01 ES009519, R01 ES009519-07A2] Funding Source: Medline
- NINDS NIH HHS [P50 NS038367, T32 NS07449-05, P50NS38367, T32 NS007449] Funding Source: Medline
Ataxia telangiectasia (AT) is an autosomal recessive disorder characterized by immunodeficiency, neurodegeneration and cancer. The disease results from bi-allelic mutations in the AT mutated (ATM) gene involved in cell cycle checkpoint control and repair of DNA double-strand breaks. Evidence has been accumulating that oxidative stress is associated with AT and may be involved in the pathogenesis of the disease. This led to a hypothesis that antioxidants may alleviate the symptoms of AT. Consequently, several studies were conducted in Atm deficient mice to examine the role of antioxidants in cancer prevention and/or correction of neuromotor performance. N-acetyl-L-cysteine (NAC), EUK-189, tempol, and 5-carboxy-1,1,3,3-tetramethylisoindolin-2-yloxyl (CTMIO) have been tested in Atm deficient mice. In contrast to other antioxidants, NAC has been used in the clinical practice for many decades and is available as a dietary supplement. In this article, we review chemoprevention studies in Atm deficient mice and, in more detail, our findings on the effect of NAC. Our short-term study showed that NAC suppressed genome rearrangements linked to cancer. The long-term study demonstrated that NAC reduced the incidence and multiplicity of lymphoma and improved some aspects of motor performance. (c) 2007 Published by Elsevier Ltd.
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