<Originals>Comparative effects of three nitrosourea derivatives on cell cycle kinetics

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Three nitrosourea derivatives (ACNU, BCNU and MCNU) were examined for effects on cell kinetics in L1210 cells and HeLa cells of maintained cultures. The inhibitory effect on cell growth was observed in the concentrations of 10μg/ml or more dose-dependently, and the intensity of the effect decreased in the order of BCNU, ACNU and MCNU. With regard to cycle specificity, ACNU and MCNU were sensitive to log phase cells, and BCNU, both to log and plateau phase cells almost equally. As to cell cycle progression, ACNU accumulated S phase cells in low concentrations but G_2+M phase cells in higher concentrations ; BCNU accumulated G_2+M phase cells and produced a polyploidy peak corresponding to 8C in 10μg/ml, but discontinued cell cycle progression in 100μg/ml, and MCNU showed to accumulate G_2+M phase cells in 1μg/ml and increasingly enhanced the cell accumulation with the increase in concentration. Inhibitory effect of DNA synthesis showed to be observed in 1 and 0.1μg/ml of ACNU, BCNU and MCNU, respectively. Higher concentrations enhanced the inhibitory effect of the individual drugs. All the drugs gave lower inhibitory effect on RNA synthesis than on DNA synthesis. Protein synthesis was slightly inhibited by higher doses of each drug. As to phase specificity, BCNU and MCNU were relatively sensitive to S phase cells and ACNU was sensitive to G_1 phase cells.
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