Blumer J L, Simpson J M, Lucas S V, Webster L T
J Pharmacol Exp Ther. 1980 Mar;212(3):509-13.
The lethal potency of the antischistosomal agent niridazole (NDZ) was compared in C57BL/6J (B6) and DBA/2J (D2) mice and in their F1 hybrid, backcross and F2 progeny. A daily i.p. dosage range was chosen so that the lethal effect, ascribed to central nervous system toxicity, did not occur before 4 to 5 days. Death was always preceded by a generalized tonic-clonic seizure which terminated in respiratory arrest. In B6 mice the LD50 was 202 mg kg-1 day-1 while in D2 mice the LD50 was 146 mg kg-1 day-1; the LD50 for NDZ in similarly treated F1 hybrid mice was found to be the arithmetic mean of the LD50 values for the parental strains (172 mg kg-1 day-1). Determination of the level of NDZ in the plasma and brains of B6 and D2 mice treated subacutely with the same daily dose of NDZ failed to reveal any strain differences. Moreover, there was no evidence of in vivo accumulation of NDZ with subacute treatment which suggests that a NDZ metabolite is responsible for the observed toxicity. An association between susceptibility to the lethal effects of NDZ and the Ah locus is suggested by experiments in backcross and F2 mice. The incidence of death observed after subacute treatment with 162 mg/kg-1 day-1 of NDZ matched that predicted on the basis of genotype, i.e., it was lethal to 72% of nonresponsive and 38% of aromatic hydrocarbon responsive mice.
比较了抗血吸虫药硝唑咪（NDZ）对C57BL/6J（B6）小鼠、DBA/2J（D2）小鼠及其F1杂种、回交和F2后代的致死效力。选择了每日腹腔注射剂量范围，以便归因于中枢神经系统毒性的致死效应在4至5天之前不会出现。死亡前总是先出现全身性强直阵挛性惊厥，最终导致呼吸停止。在B6小鼠中，半数致死剂量（LD50）为202毫克/千克/天，而在D2小鼠中，LD50为146毫克/千克/天；在同样处理的F1杂种小鼠中，NDZ的LD50被发现是亲本品系LD50值的算术平均值（172毫克/千克/天）。对以相同日剂量NDZ进行亚急性处理的B6和D2小鼠的血浆和脑中NDZ水平的测定未能揭示任何品系差异。此外，亚急性处理没有NDZ体内蓄积的证据，这表明NDZ的一种代谢产物是观察到的毒性的原因。回交和F2小鼠的实验表明，对NDZ致死效应的易感性与Ah位点之间存在关联。用162毫克/千克/天的NDZ进行亚急性处理后观察到的死亡发生率与基于基因型预测的发生率相符，即对72%的无反应小鼠和38%的芳烃反应小鼠具有致死性。
