INCREASED APOPTOTIC RESPONSE TO 2-DEOXY-D-RIBOSE IN ATAXIA-TELANGIECTASIA

Ataxia-telangiectasia (AT) is an autosomal recessive disease character ized by neurodegeneration and immunodeficiency. Hypersensitivity to ra diation and chromosome instability are the biological markers of this disease. The gene responsible for AT (ATM)I has been identified on chr omosome 11q22-23; it encodes a large polypeptide partially homologous to the phosphatidylinositol (PI) 3-kinase family. PI 3-kinase is a pro tein family playing an important role in the prevention of apoptosis. In order to investigate the apoptosis pathway, we tested peripheral bl ood cells from AT patients and controls exposed to 2-deoxy-D-ribose (d Rib), a reducing sugar that induces apoptosis in human quiescent lymph ocytes, probably through oxidative damage. Our results show that the r esponse to dRib-induced apoptosis is significantly more elevated in AT cells than in control cells, suggesting that the apoptotic process pl ays a role in the pathogenesis of AT disease.