[Effect of ACNU, a water-soluble nitrosourea derivative, on survival and cell progression of cultured HeLa S3 cells].

Effects of a water-soluble nitrosourea derivative, 1-(4-amino-2-methylpyrimidin-5-yl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride [ACNU]. on survival and cell progression of HaLe S3 cells was investigated. The survival of exponentially growing cells exposed to increasing concentrations of the drug was characterized by a threshold-type survival curve (D0 = 7.0 micrograms/ml X 1 hr, Dq = 3.5 micrograms/ml X 1 hr). ACNU exerted its main killing effect on cells in G1 and G2 + M phases, whereas cells in S phase were resistant to the drug. Changes in survival response as a function of cell cycle were mainly dependent upon the extent of the exponential slope of the survival curve. Cell progression effects were examined by using a low concentration of ACNU in which 80% of treated cells could survive. Cells in G1 and early S phases at the time of treatment were not prevented from entering S phase but prolonged in duration of S phase followed by a marked delay in progression through G2 phase. However, such a delay in cell progression time was reduced in cells treated in mid S phase as compared with G1 and early S phases. Cells treated in late S and G2 phases could normally progress into mitosis.