| Abstract: | The cytotoxic action of 2-thiouracil, 2-thiocytosine, 2-thiouridine and 4-thiouridine was studied in cultures of a clone of Chinese hamster cells with a generation time of 16 hours (S — 8 hours, G2 — 2 hours, and G1 plus M — 6 hours). The cells were synchronized at metaphase by the method of reversal of colcemid inhibition and cell survival was measured by their colony-forming ability. The four analogs induced cytotoxic effects which increased with the concentration of the chemical and the length of the exposure time. Exposure to 4 × 10?4 M 2-thiocytosine, 2-thiouridine or 4-thiouridine for a period of 20 hours reduced cell survival to less than 10% of the controls. The other analog (2-thiouracil) was less effective when tested at similar concentrations and time of exposure and decreased the survival to only 35% of the controls. Short periods of treatment (one hour) produced little effect at concentrations of 4 × 10?5M, and affected the survival of cells differently when 4 × 10?4 M were administered at different stages of the cell cycle. Two peaks of maximum sensitivity, one at late G1 and the other at G2 were observed. These peaks correspond to the peaks of maximum RNA synthesis described for synchronized mammalian cells. Therefore, it is likely that the cytotoxic effects of thiopyrimidine analogs are related to interference with RNA synthesis. |
