Effects of combined exposure to thaliblastine and gamma rays on DNA, RNA, and protein synthesis in leukocytes from rat peripheral blood

The action of the alkaloid thaliblastine (a Bulgarian potential antitumor drug) upon macromolecule synthesis has been studied in vitro by treating rat peripheral leukocytes with the agent solely or combined with irradiation. The concentration tested were 1, 5, 10, 15, and 20 μg/ml blood, which are sublethal to the cells. A 137Cs gamma source was used to deliver a single dose of 1, 2, 3, or 4 Gy. For combined exposures, the blood was exposed to a 2 Gy dose and simultaneously treated with thaliblastine. The changes in macromolecule synthesis were judged by recording incorporation of labelled precursors relative to that in non-treated controls taken as 100%. With sole thaliblastine treatments, most markedly suppressed was protein synthesis. Radiation alone inhibited to the largest extent the synthesis of DNA. With combined treatments, DNA synthesis was again the most markedly affected of the three synthesis types; the inhibitory effect proved additive, with a tendency to potentiation in the case of higher thaliblastine concentrations. Suppression of protein synthesis was less pronounced that expected on a hypothetic additivity basis. The changes observed in macromolecule synthesis under sole or combined action of thaliblastine and gamma rays indicated the two types of cytostatics to differ in mechanisms of action. For radiation, the target was DNA, whereas for thaliblastine the cell division spindle appeared to be the most likely target. The evidence obtained with combined exposure pointed to the determining role of radiation as a factor interfering with macromolecule synthesis. (author)