[Effect of ACNU, a water-soluble nitrosourea, on cell cycle of cultured glioma cells--flow cytometric analysis].
Cytotoxic and cytokinetic effects of 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl) 3-nitrosourea hydrochloride (ACNU) on cultured rat and human glioma cells (C-6 and KC) were studied in vitro. Exponentially growing culture cells were exposed to ACNU at the final concentrations of 5 micrograms/ml, 20 micrograms/ml, and 80 micrograms/ml, respectively. The cytotoxic effect was evaluated by inhibition of cell growth and the cytokinetic effect was analyzed by DNA histogram using a flow cytometer. Inhibition of cell growth was dose-dependent in ACNU and C-6 cells were more resistant than KC cells. The growth of C-6 and KC cells were not inhibited at all by low concentrations of ACNU (5 micrograms/ml, 20 micrograms/ml), however, at these concentrations a marked accumulation of treated cells in S and G2+ M phases was evident. The accumulation in S and G2+M phases was dose-dependent and it was more prominent in KC than C-6 cells. ACNU-treated cells accumulated initially in S phase and then in G2+M phase. After maximum accumulation in G2+M phase, the cells seemed to be released into G1 or G0 phase. These results indicate that the cytokinetic effect of ACNU (5 micrograms/ml, 20 micrograms/ml) is more conspicuous than the cytotoxic effect on C-6 and KC cells.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D005910:Glioma / Q000473:pathology*; D006801:Humans; D008938:Mitosis / Q000187:drug effects; D015376:Nimustine; D009607:Nitrosourea Compounds / Q000494:pharmacology*; D051381:Rats
D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; D015376:Nimustine