丝裂霉素C和/或光化学疗法对人结肠腺癌细胞系的细胞毒性和细胞动力学效应

Cytotoxicity and cytokinetic effects of mitomycin C and/or photochemotherapy in a human colon adenocarcinoma cell line.

Ma L W, Steen H B, Moan J, Berg K, Peng Q, Saether H, Rimington C

Department of Biophysics, Institute for Cancer Research, Montebello, Oslo, Norway.

Int J Biochem. 1992 Nov;24(11):1807-13. doi: 10.1016/0020-711x(92)90132-k.

Abstract

The cytotoxicity and cytokinetic effects of Mitomycin C (MC) and/or photochemotherapy (PCT) in cultured human colon adenocarcinoma (WiDr) cells were investigated using colony formation to determine cell survival and DNA flow cytometry to analyze cell kinetics. 2. A low concentration of MC (0.01 micrograms/ml) caused accumulation of cells in late S and early G2 phase; higher concentrations (0.05-0.5 micrograms/ml) induced accumulation of the cells in mid and early S phase. 3. The effects of the lowest concentration of MC (0.01 micrograms/ml) were reversible upon removal of the drug, whereas a higher concentration of MC (0.1 micrograms/ml) resulted in a permanent inhibition of cell cycle progression. 4. The sensitivity of Photofrin II-loaded cells to PCT can be enhanced significantly by the addition of MC. 5. The MC-induced accumulation of the cells in S phase may be one reason for the increased cytotoxicity of PCT combined with MC. 6. The data suggest that MC may also inhibit repair of PCT-induced DNA damage.

摘要

利用集落形成法测定细胞存活率，采用DNA流式细胞术分析细胞动力学，研究了丝裂霉素C（MC）和/或光化学疗法（PCT）对培养的人结肠腺癌（WiDr）细胞的细胞毒性和细胞动力学效应。2. 低浓度的MC（0.01微克/毫升）导致细胞在S期晚期和G2期早期积累；较高浓度（0.05 - 0.5微克/毫升）诱导细胞在S期中期和早期积累。3. 去除药物后，最低浓度的MC（0.01微克/毫升）的作用是可逆的，而较高浓度的MC（0.1微克/毫升）导致细胞周期进程的永久性抑制。4. 添加MC可显著增强负载光敏素II的细胞对PCT的敏感性。5. MC诱导细胞在S期积累可能是PCT联合MC细胞毒性增加的原因之一。6. 数据表明，MC也可能抑制PCT诱导的DNA损伤的修复。