TOXICOGENETICS OF NIRIDAZOLE IN INBRED MICE

  • 1 January 1980
    • journal article
    • research article
    • Vol. 212  (3) , 509-513
Abstract
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 CNS toxicity, did not occur before 4-5 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 per day while in D2 mice the LD50 was 146 mg/kg per day; the LD50 for NDZ in similarly treated F1 hybrid mice was the arithmetic mean of the LD50 values for the parental strains (172 mg/kg per day). 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. 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 and 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 per day of NDZ matched that predicted on the basis of genotype, i.e., it was lethal to 72% of nonresponsive and to 38% of aromatic hydrocarbon responsive mice.