Effects of 3′-deoxy-3′-fluorothymidine on proliferation kinetics of Ehrlich ascites tumour cells in vitro (comparison with other cytostatic drugs)

Abstract

Treatment of Ehrlich ascites carcinoma cells in vitro with cytosine-arabinoside, 5-fluoro- 2′-deoxyuridine and hydroxyurea in concentrations just completely inhibiting cell proliferation, results, in agreement with data published for other cells, in progressive loss of viability if the treatment exceeds a period of one generation time (about 14hr). Pulse cytophotometric analysis of the treated cells showed them to be located mainly in the G 1 -phase of the cell cycle. In contrast, cell proliferation can be inhibited for about 32hr (more than 2 generation times), without loss of viability, if the treatment is done with 3′-deoxy- 3′-fluorothymidine ( 3′-FTdR). Pulse cytophotometric analysis revealed a concentration-dependent delay of progression through the S-phase. At a concentration just completely inhibiting cell proliferation, discontinuation of proliferation was predominant in late S-phase at the G 2 -boundary. These properties recommend 3′-FTdR for experiments aimed at improving cancer chemotherapy by a non-toxic accumulation of cells in the S-phase followed by treatment with a second, S-phase specific agent.