Antioxidants suppress lymphoma and increase longevity in Atm-deficient mice.
Ataxia telangiectasia (AT), a human hereditary disorder resulting from mutations in the ATM gene, is characterized by a high incidence of lymphoid malignancies, neurodegeneration, immunodeficiency, premature aging, elevated radiosensitivity, and genomic instability. Evidence has been accumulating that ATM-deficient cells are in a continuous state of oxidative stress. A variety of markers of oxidative stress were detected in AT patients as well as Atm-deficient mice, used as an animal model of AT. Since then, it has been proposed that oxidative stress contributes to the clinical phenotype of AT, especially carcinogenesis and neurodegeneration, and several animal studies were conducted to determine whether exogenous antioxidants mitigate the symptoms of AT. Tempol, EUK-189, and N-acetyl cysteine have been tested as chemopreventive antioxidants in Atm-deficient mice. We review these findings, mainly focusing on the effect of N-acetyl cysteine, which is known as a safe and efficient drug and nutritional supplement.
Reliene
Ramune
R
Department of Pathology, Geffen School of Medicine and School of Public Health, University of California, Los Angeles, CA 90095, USA.
Schiestl
Robert H
RH
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008136:Longevity / Q000187:drug effects* / Q000502:physiology; D008223:Lymphoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*
D000975:Antioxidants; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases; D000111:Acetylcysteine