ABSTRACT
Abstract A tm deficient (Atm~hyAtmyly and^/w-ASRI) mice closely mimic most of the phenotype of
Z J human ataxia telangiectasia (AT). This includes growth retardation, immunodeficiency, ^ Z J L infertility, genomic instability, acute sensitivity to ionizing radiation and a striking predis position to lymphoid malignancies. However, Atm deficient mice do not recapitulate cerebellar degeneration and show only a mild form of ataxia. Nevertheless, Atm deficient mice provided researchers the first opportunity to study AT in a controlled way in mammals and in multiple tis sues. Studies with Atm deficient mice revealed most of our understanding of the role of oxidative stress in AT. Consequendy, oxidative stress has been viewed as a potential mechanism contributing to the clinical manifestations of AT. Thus, Atm deficient mice have been used to study the effect of antioxidants, as a new therapeutic approach to treat AT. These studies showed that antioxidants N-Acetyl-L-Cysteine (NAC), EUK-189, tempol and CTM IO are able to correct some cellular and clinical phenotypes of AT. In particular, antioxidants were efficient in preventing lymphomagenesis. An ongoing clinical trial (Thomas Jefferson University Medical College) and future chemoprevention trials in AT patients, will provide more evidence as to whether antioxidant intake can slow down disease progression in AT.
