Chao C F, Subjeck J R, Johnson R J
Br J Radiol. 1983 Jan;56(661):27-31. doi: 10.1259/0007-1285-56-661-27.
The hypoxic cell radiosensitiser desmethylmisonidazole (DMM, Ro-05-9963) was administered orally to C3Hf female mice at three different dose levels (1.4, 1.6 and 1.8 mg g-1 day-1). Behavioural and morphological end-points were used to evaluate the neurotoxicity of this compound at these doses. The behavioural changes present at all three dose levels appeared when the total dose approached approximately 19 mg g-1. The behavioural changes initially appeared and developed to a severe state rapidly (24 to 48 h). A pattern of haemorrhagic necrosis was observed in the brain stem and cerebellum, but no pathology was observed in the cerebrum. Peripheral nerve degeneration was also evident and appeared concurrent with the central pathology. DMM appears to affect both the central and peripheral nervous systems at the same time at these dose levels. This is in some degree different from previous experience with misonidazole where peripheral damage distinctly precedes central effects. The development of the disorder appeared to be more rapid and severe when compared with earlier experience with misonidazole.
对C3Hf雌性小鼠口服低氧细胞放射增敏剂去甲基米索硝唑（DMM，Ro-05-9963），剂量分为三个不同水平（1.4、1.6和1.8mg g-1天-1）。行为和形态学终点用于评估该化合物在这些剂量下的神经毒性。当总剂量接近约19mg g-1时，在所有三个剂量水平均出现行为变化。行为变化最初出现，并迅速发展至严重状态（24至48小时）。在脑干和小脑中观察到出血性坏死模式，但在大脑中未观察到病理学变化。周围神经变性也很明显，与中枢病理学变化同时出现。在这些剂量水平下，DMM似乎同时影响中枢和周围神经系统。这在某种程度上与之前米索硝唑的经验不同，在米索硝唑的经验中，周围损伤明显先于中枢效应。与早期米索硝唑的经验相比，该疾病的发展似乎更快、更严重。
