In vivo radiosensitization of nitroimidazole derivative [KIN-804] compared with misonidazole [MISO]

The effects of a single dose of KIN-804 and MISO on liver and Ehrlich solid carcinoma [ESC] have been studied in Swiss albino mice. KIN-804 and MISO were administered at doses of 800 and 400 mg/Kg body weight, respectively. Liver glucose-6-phosphatase [G-6-pase], glutathione content and superoxide dismutase of ESC, were measured at different times from drug administration. [G-6-pase] was elevated significantly 24 hours after MISO only, while GSH and SOD showed nearly the same changes after MISO and KIN 804. Therefore, KIN-804 is a less toxic radiosensitizer and should be implicated in clinical trials

Chemical radiosensitization by misonidazole: production and repair of DNA single-strand breaks in Yoshida ascites tumor cells.

Formation of strand-breaks in DNA and its repair in Yoshida ascites tumor cells exposed to gamma radiation (100-400 Gy) in presence and absence of misonidazole (10 mM) were studied. The methodology involved pre-labelling of cellular DNA by 3H-thymidine during cell proliferation in rats, irradiation of cells in vitro and analysing sedimentation profile of DNA by ultracentrifugation in alkaline sucrose density gradients. Irradiation under euoxic conditions resulted in formation of about 1.5 times greater number of strand breaks as compared to those formed during irradiation under hypoxic conditions. Misonidazole (10 mM) by its presence along with the cells during irradiation under hypoxic conditions caused a 3-fold increase in the number of single strand breaks, but under euoxic conditions of irradiation the presence of misonidazole did not enhance the strand break formation. Incubation of cells irradiated in absence of misonidazole for 1 hr in tissue culture medium at 37 degrees C resulted in repair of substantial fraction of the strand breaks while there was no repair of the DNA strand breaks in cells irradiated in the presence of the chemical.