Protection by glucose and derivatives against the lethal toxicity of mitomycin C in bacteria.
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.
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D002241:Carbohydrates / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003470:Culture Media; D004926:Escherichia coli / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology*; D006367:HeLa Cells / Q000187:drug effects; D006801:Humans; D007928:Lethal Dose 50; D051379:Mice; D016685:Mitomycin; D008937:Mitomycins / Q000633:toxicity*
D000903:Antibiotics, Antineoplastic; D002241:Carbohydrates; D003470:Culture Media; D008937:Mitomycins; D016685:Mitomycin; D005947:Glucose