Methylisobutylxanthine, a potent inhibitor of cAMP phosphodiesterase, enhances the sensitivity of Chinese hamster ovary cells to mitomycin C.
The effect of 1-methyl-3-isobutylxanthine (MIX) on the sensitivity of CHO cells to mitomycin C (MC) was examined. Treatment of cells with MIX before MC-exposure greatly enhanced the cellular sensitivity to MC, with no effect on plating efficiency. Treatment with MIX after MC-exposure had only a slight effect. The sensitivity to MC was enhanced, biphasically, with increases in the period of pretreatment with MIX. The sensitivity of cells to MC fluctuated through the cell cycle, in that they were most sensitive to MC in G1 and resistant in the G2/M phase. Flow cytometric studies revealed a partial accumulation of cells in G1 (12% increase) at 16 h after MIX treatment. This means that the enhanced sensitivity with MIX pretreatment may partly depend on the accumulation of the cells in G1 and which are sensitive to MC. However, other cellular processes may also be involved, since the accumulation in G1 cannot explain all of the sensitization.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology*; D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D007399:Interphase / Q000187:drug effects; D016685:Mitomycin; D008937:Mitomycins / Q000494:pharmacology*; D013806:Theophylline / Q000031:analogs & derivatives*
D008937:Mitomycins; D016685:Mitomycin; D003994:Bucladesine; D013806:Theophylline; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D015056:1-Methyl-3-isobutylxanthine