Effects of antioxidants on cancer prevention and neuromotor performance in Atm deficient mice.
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.
Department of Pathology, David Geffen School of Medicine and School of Public Health, UCLA, Los Angeles, CA 90095, USA.
Ramune
R
Reliene
Sheila M
SM
Fleming
Marie-Françoise
MF
Chesselet
Robert H
RH
Schiestl
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D016166:Free Radical Scavengers / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009369:Neoplasms / Q000517:prevention & control*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D011597:Psychomotor Performance / Q000187:drug effects*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D000975:Antioxidants; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D016166:Free Radical Scavengers; D025521:Tumor Suppressor Proteins; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases; D000111:Acetylcysteine