Nagamatsu T, Ishizawa M, Taniguchi S, Iwamoto Y, Kawano T, Baba T
Jpn J Antibiot. 1985 Jul;38(7):1761-8.
Agents capable of preventing the toxicity of mitomycin C (MMC) were investigated by a cytotoxicity assay utilizing the E. coli strain WP2 uvrA, a strain sensitive to the bactericidal action of MMC. Of various compounds, mixtures, and rat tissue extracts assayed, the solution of liver extracts and yeast extracts and DULBECCO's modified EAGLE's medium (DMEM) exhibited potent activity in protecting the cells against the MMC toxicity. A further analysis of the individual components of DMEM revealed that glucose is the active principle responsible for the protection seen with DMEM. A similar protection has been observed with the use of mannose, mannitol, 2-deoxyglucose, D-glucuronic acid, glucosamine, and N-acetylglucosamine of 16 sugar derivatives tested. The protection by glucose was specific to treatment of cells with MMC but not with UV-irradiation, cis-diamminedichloroplatinum (II), 4-nitroquinoline 1-oxide, or furylfuramide. Unlike the bacterial cells, there was no protective response in the mammalian cells in culture and in mice, given a lethal dose of MMC, concurrently with glucose or each derivative. The possible mechanisms involved in this prevention of MMC toxicity by glucose are discussed.
利用对丝裂霉素C(MMC)杀菌作用敏感的大肠杆菌菌株WP2 uvrA,通过细胞毒性试验研究了能够预防MMC毒性的药物。在所检测的各种化合物、混合物和大鼠组织提取物中,肝提取物、酵母提取物和杜氏改良伊格尔培养基(DMEM)的溶液在保护细胞免受MMC毒性方面表现出强大的活性。对DMEM单个成分的进一步分析表明,葡萄糖是导致DMEM所见保护作用的活性成分。在所测试的16种糖衍生物中,使用甘露糖、甘露醇、2-脱氧葡萄糖、D-葡萄糖醛酸、氨基葡萄糖和N-乙酰氨基葡萄糖也观察到了类似的保护作用。葡萄糖的保护作用对用MMC处理细胞具有特异性,但对紫外线照射、顺二氨二氯铂(II)、4-硝基喹啉1-氧化物或呋喃糠酰胺处理细胞则无特异性。与细菌细胞不同,在培养的哺乳动物细胞和给予致死剂量MMC的小鼠中,同时给予葡萄糖或每种衍生物时,没有观察到保护反应。本文讨论了葡萄糖预防MMC毒性可能涉及的机制。