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Objective To investigate the relationship between the intracellular glutathione (GSH) and the cytotoxicity of two alkylating agents, nitrogen mustard and cisplatin, in the human leukemia (HL) 60 and gastric cancer (SGC) 7901 cell lines Methods The cytotoxicity of the alkylating agents was evaluated using the modified tetrazolium dye assay The total cellular content of glutathione was determined by the modified method of Tietze Results In the HL 60 cells, 50 μmol/L buthionine sulfoximine, a glutathione synthesis inhibitor, depleted the cellular glutathione by about 90% Such depletion greatly increased the cytotoxicity of nitrogen mustard, with the cell survival rate reducing from 70 0% to 40 0% A strong inverse correlation was identified between the nitrogen mustard cytotoxicity and the cellular glutathione levels modulated with buthionine sulfoximine ( r =0 98) However, the cytotoxicity of nitrogen mustard in the cells with 70% glutathione remaining was similar to that in the control cells with an intact glutathione pool In the SGC 7901 cells, significant enhancement of the cisplatin cytotoxicity was observed after the extensive glutathione depletion (by about 90%), and such effect was more pronounced in the hypoxic cells than in the aerobic cells (dose modifying factors, 2 62 vs 1 87) Conclusions The cellular glutathione plays an important role in the expression of the alkylating agent cytotoxicity in the HL 60 cells, and the aerobic or the hypoxic SGC 7901 cells
Objective To investigate the relationship between the intracellular glutathione (GSH) and the cytotoxicity of two alkylating agents, nitrogen mustard and cisplatin, in the human leukemia (HL) 60 and gastric cancer (SGC) 7901 cell lines Methods The cytotoxicity of the alkylating agents was Evaluation using the modified tetrazolium dye assay The total cellular content of glutathione was determined by the modified method of Tietze Results In the HL 60 cells, 50 μmol/L buthionine sulfoximine, a glutathione synthesis inhibitor, depleted the cellular glutathione by about 90% Such depletion Largely increasing the cytotoxicity of nitrogen mustard, with the cell survival rate reducing from 70 0% to 40 0% A strong inverse correlation was identified between the nitrogen mustard cytotoxicity and the cellular glutathione levels modulated with buthionine sulfoximine ( r =0 98) The cytotoxicity of nitrogen mustard in the cells with 70% glutathione remaining was simi Lar to that in the control cells with an intact glutathione pool In the SGC 7901 cells, significant enhancement of the cisplatin cytotoxicity was viewed after the extensive glutathione depletion (by about 90%), and such effect was more pronounced in the hypoxic cells than in The aerobic cells (dose modifying factors, 2 62 vs 1 87) Conclusions The cellular glutathione plays an important role in the expression of the alkylating agent cytotoxicity in the HL 60 cells, and the aerobic or the hypoxic SGC 7901 cells