betaS Chain turnover in reticulocytes of sickle trait individuals with high or low concentrations of haemoglobin S.

Reticulocytes, isolated from the blood of sickle cell trait donors with either low (25-30%) or high (40-42%) haemoglobin S(Hb S) concentrations, were incubated with [3H]leucine for various times from 1.25 to 60 min. Samples of the total soluble fractions of the cells were denatured with urea and mercaptoethanol. The mixtures were analysed by electrophoresis on cellulose acetate strips. The specific radioactivities (dpm/mg) of the separated betaS and betaA globin chains were determined. The betaS/betaA ratios of globin chain specific radio activities in the reticulocytes of the 'low Hb S' donors decreased gradually from initial values higher than 1.30 to values near unity. These data suggested that faster turnover of some of the soluble, newly synthesized betaS chains compared to the newly synthesized betaA chains could explain part, but not all, of the disparity in concentrations of Hbs S and A in these people. When reticulocytes from 'high Hb S' donors were 3H-labelled for times longer than 5 min, the betaS/betaA specific radioactivity ratios remained at or near unity. This result suggested that newly synthesized betaS chains were not turning over selectively in these cells. Instead, there was a relative decrease in betaS chain synthesis proportional to the difference in blood concentrations of Hb S and Hb A. Additional calculations suggested that the more rapid turnover of newly synthesized betaS chains in the 'low Hb S' reticulocytes could explain the difference in Hb S concentrations between 'high and low Hb S' people. These results are consistent with previous reports that an alpha-thalassaemia gene, present in 'low Hb S' but absent in 'high Hb S' donors, may be responsible for the selective turnover of betaS chains.