INCREASED IFN-ALPHA-INDUCED SENSITIVITY BUT REDUCED REACTIVITY OF 2',5'-OLIGOADENYLATE SYNTHETASE (2,5AS) IN TRISOMY-21 BLOOD-LYMPHOCYTES

2,5AS is induced by interferon-alpha, -beta (IFN-alpha, -beta) and pol ymerizes adenosine triphosphate (ATP) into pppA (2'p5'A) oligomers, le ading to inhibition of protein synthesis and virus growth. The gene co ding for the IFN-alpha, -beta receptor is localized to chromosome 21. In trisomy 21 cells from patients with Down's syndrome a 50% increase in gene dosage is present for the genes on this chromosome. Correspond ing increase of gene products has been shown for several of these gene s, e.g. the IFN-alpha, -beta receptor molecules. Here, we show a direc t proportionality between the number of IFN-alpha, -beta receptors and both the basal activity of 2,5AS and the sensitivity of this enzyme f or IFN-alpha, -beta. The relative increase of 2,5AS activity (the reac tivity) becomes reduced consistent with the increased basal 2,5AS acti vity in trisomy 21 cells compared with control cells.