Increased susceptibility of fibroblasts from horses with severe combined immunodeficiency to growth inhibition by 2'-deoxyadenosine.

The effect of adenosine, deoxyadenosine, guanosine, and deoxyguanosine on the growth rate of fibroblasts derived from normal horses, horses heterozygous for the severe combined immunodeficiency (SCID) trait (heterozygotes), and horses with SCID was studied. All four purines were found to inhibit growth in a dose-dependent manner, but only adenosine and deoxyadenosine were inhibitory at concentrations of less than 100 microM. No statistical difference in sensitivity to adenosine was detected between normal and SCID fibroblasts. Fibroblasts from SCID horses were, however, more sensitive to the growth inhibitory effects of deoxyadenosine than were fibroblasts from normal horses. Furthermore, following 24 hr of incubation with radiolabeled deoxyadenosine, radiolabeled deoxyATP concentrations were found to be twofold higher in SCID fibroblasts compared to those concentrations measured in normal fibroblasts cultured under identical conditions. Adenosine deaminase and S-adenosylhomocysteine hydrolase activities were normal in SCID fibroblasts. These findings suggest that SCID horses may have a defect in either transport or phosphorylation of deoxyadenosine, or in the utilization of deoxyATP.