Effect of misonidazole on the radiosensitivity and repair of potentially lethal damage of L5178Y ascites tumor cells.
The radiosensitizing effect of low concentrations of misonidazole was investigated by using L5178Y cells growing as an ascites tumor in DBA-2 mice. The cells were irradiated in vivo with graded doses of X-rays in the presence or absence of 0.1-0.5 mg/g body weight of misonidazole. Then cell survival was assayed in vitro by plating cells in soft agar medium. By analyzing the X-ray survival curves with or without misonidazole, the dose-modifying effects were determined. The results indicated that the slope and shoulder of the survival curves were greatly modified by the treatment with misonidazole. The dose-modifying factor in terms of the D0 ratio between the drug-treated and untreated control cells was increased as the drug concentration was increased. Further, it was revealed that the isoeffect dose ratios, estimated by the linear quadratic equation of Chadwick and Leenhouts, were higher at a low-radiation dose range. This is due to the suppression of the shoulder region of survival curves for the drug-treated cells. The inhibition of the X-ray-induced repair of potentially lethal damage was apparent with 0.1 mg/g body weight of misonidazole. The inhibition became more effective as the drug concentration increased.
D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D007940:Leukemia L5178 / Q000473:pathology*; D007942:Leukemia, Experimental / Q000473:pathology*; D051379:Mice; D008811:Mice, Inbred DBA; D008920:Misonidazole / Q000494:pharmacology* / Q000633:toxicity; D009593:Nitroimidazoles / Q000494:pharmacology*; D010100:Oxygen; D011836:Radiation Tolerance
D009593:Nitroimidazoles; D008920:Misonidazole; D010100:Oxygen