Kai Kiyonori, Sahto Hiroshi, Yoshida Mitsuyoshi, Suzuki Takami, Shikanai Yukari, Kajimura Tetsuyo, Furuhama Kazuhisa
Drug Safety Research Laboratory, Daiichi Pharmaceutical Company Ltd., Tokyo, Japan.
Toxicol Pathol. 2006;34(3):223-31. doi: 10.1080/01926230600695557.
Species and sex differences in susceptibility to vincristine sulphate (VCR)-induced olfactory epithelial lesions were investigated among the BALB/c mice, Crj: CD(SD) IGS rats and common marmoset monkeys following a single intravenous administration on day 1. As dosage levels, the 0.17-fold LD10, 0.6-fold LD10 and LD10 were used for mice and rats, and a maximum tolerated dose (MTD) was chosen only for monkeys. The order of strength of VCR action on peripheral neuropathic signs, body weight gain, and hematological parameters was mice > rats > monkeys, without clear sex differences. Histopathologically, on day 2, single cell death in the olfactory epithelium and vomeronasal organ was observed only in male mice at LD10, and in female mice at 0.6-fold LD10 or more. On day 5, the olfactory epithelium in these mice showed regenerative proliferation suggesting a sign of recovery. On day 10, axonopathy and demyelination in the sciatic and trigeminal nerves were noted in mice of both sexes at 0.6-fold LD10 or more. In rats and monkeys of either sex, however, no morphological changes were observed at any dose level. In conclusion, mice, particularly females, were shown to be more susceptible to VCR-induced apoptosis in the olfactory epithelium than rats and monkeys.
在第1天单次静脉注射后，研究了BALB/c小鼠、Crj:CD(SD)IGS大鼠和普通狨猴对硫酸长春新碱（VCR）诱导的嗅觉上皮损伤易感性的物种和性别差异。作为剂量水平，小鼠和大鼠分别使用0.17倍LD10、0.6倍LD10和LD10，而仅为猴子选择了最大耐受剂量（MTD）。VCR对外周神经病变体征、体重增加和血液学参数作用强度的顺序为小鼠>大鼠>猴子，无明显性别差异。组织病理学上，在第2天，仅在LD10的雄性小鼠以及0.6倍LD10及以上的雌性小鼠中观察到嗅觉上皮和犁鼻器中的单细胞死亡。在第5天，这些小鼠的嗅觉上皮显示出再生增殖，提示恢复迹象。在第10天，0.6倍LD10及以上的两性小鼠坐骨神经和三叉神经中均出现轴突病和脱髓鞘。然而，在任何剂量水平下，无论雌雄，大鼠和猴子均未观察到形态学变化。总之，小鼠，尤其是雌性小鼠，对VCR诱导的嗅觉上皮细胞凋亡比大鼠和猴子更敏感。
