Effect of dexamethasone hemisulfate on nucleic acid synthesis in human granulocytes

Abstract

Dexamethasone hemisulphate (Dexa-Scheroson®) concentrations of 100 <i>μ</i>/ml culture medium produces a marked inhibition of the incorporation of ¹⁴C-adenine into the trichloroacetic acid precipitate and nucleic acids of granulocytes. Exact analysis of the precursor pool and measurement of the rate of nucleic acid synthesis showed that this inhibition of incorporation by the dexamethasone ester was due to a reduction in the formation of fresh nucleic acids. Fractionation of these extracts in linear sucrose gradients revealed a remarkable diminution in the radioactivity of the fractions 18 S and 4 S. We believe the cause of this change in metabolism could be that a false ribosomal RNA precursor is formed which does not contain the 18S portion. Alternatively, one might postulate an increased instability of this component. Such changes could lead to a reduction in existing ribosomes and in protein synthesis. In this case, the diminished turnover of transfer nucleic acids, perhaps corresponding to the component sedimenting at 4S, could be interpreted as a further rational biological reaction.