Effect of a hypoxic cell sensitizer doranidazole on the radiation-induced apoptosis of mouse L5178Y lymphoma cells.
We investigated the sensitizing effect of the 2-nitroimidazole analogue doranidazole, a new hypoxic radiosensitizer, on radiation-induced apoptosis in L5178Y cells. Apoptosis was assessed by checking DNA ladder formation, the presence of sub-G1 peaks in flow cytometry, and chromatin condensation. A radiosensitizing effect of doranidazole was also confirmed by a soft-agar colony assay of surviving cells. In the assay of DNA ladder formation, DNA fragmentation was observed following irradiation under an aerobic or hypoxic condition with or without doranidazole. The proportions of the cells at the sub-G1 peak in a flow cytometric measurement was not very different among the irradiations at 5 Gy under the aerobic condition, 15 Gy under hypoxia, and 10 Gy with 1 mM doranidazole under hypoxia. The fraction of cells with chromatin condensation was found to be significantly increased with doranidazole up to 3 mM when applied under hypoxic irradiation, but did not increase even at 10 mM. The sensitizer enhancement ratio was estimated to be about 1.7 with a concentration of 1 mM. This enhancement ratio was not different from that observed by assaying cell survivals. On the other hand, doranidazole showed no radiosensitizing effect under aerobic conditions with 1 mM. In conclusion, the radiation-induced apoptosis of L5178Y cells was enhanced by doranidazole under hypoxia.
Aoki
Mizuho
M
Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan. mizuho@nirs.go.jp
Furusawa
Yoshiya
Y
Shibamoto
Yuta
Y
Kobayashi
Ataru
A
Tsujitani
Michihiko
M
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D007093:Imidazoles / Q000627:therapeutic use*; D008223:Lymphoma / Q000503:physiopathology* / Q000532:radiotherapy*; D051379:Mice; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D007093:Imidazoles; D011838:Radiation-Sensitizing Agents; C106738:doranidazole