Kishino Y
Nihon Sanka Fujinka Gakkai Zasshi. 1983 Dec;35(12):2368-76.
It is already known that Misonidazole as a radiosensitizer is not so effective with the small doses of radiation that we generally use to treat human uterine cervical carcinoma by fractionated irradiation. Using nude mice in which human uterine cervical carcinoma was transplanted, we examined DNA distribution by Flow-Microfluorometry, nuclear area and growth curves with 1,000 rads single dose irradiation, equally fractionated irradiation (250 rads/day for 4 days) and unequally fractionated irradiation (250 rads/day for 4 days, 500 rads for 1 day) after administration of Misonidazole. It was recognized that repopulation was delayed with 1,000 rads single dose irradiation with Misonidazole 1 mg/g.b.w. since a reduction in the rate of increase in G2-M cells and an increase in debris lasted a long time in DNA distribution, and the tumor regrowth time was delayed when compared to the only irradiation group. These changes were not observed with equally fractionated irradiation with Misonidazole 0.25 mg/g.b.w/day administration, but were significantly observed with unequally fractionated irradiation with Misonidazole 1 mg/g.b.w. at 500 rads irradiation where the nuclear area was also reduced. As mentioned above, it can be considered that the clinical effect of Misonidazole can be expected as in the case of unequally fractionated irradiation.
已知作为放射增敏剂的米索硝唑,对于我们通常用于分次照射治疗人类子宫颈癌的小剂量辐射,效果并不理想。我们使用移植了人类子宫颈癌的裸鼠,在给予米索硝唑后,通过流式细胞荧光测定法检测DNA分布、核面积以及用1000拉德单次剂量照射、均匀分次照射(250拉德/天,共4天)和不均匀分次照射(250拉德/天,共4天,1天500拉德)后的生长曲线。结果发现,用1毫克/克体重的米索硝唑进行1000拉德单次剂量照射时,再增殖延迟,因为在DNA分布中G2-M期细胞增加率降低且碎片增加持续了很长时间,与仅照射组相比,肿瘤再生长时间延迟。用0.25毫克/克体重/天的米索硝唑进行均匀分次照射时未观察到这些变化,但在用1毫克/克体重的米索硝唑进行不均匀分次照射且500拉德照射时核面积也减小的情况下,显著观察到了这些变化。如上所述,可以认为米索硝唑的临床效果有望如在不均匀分次照射的情况下那样。