Takeno S, Sumita M, Saito H, Sakai T
Department of Toxicology, School of Pharmacy, Hokuriku University, Kanazawa, Japan.
Res Commun Chem Pathol Pharmacol. 1987 Sep;57(3):409-19.
Embryotoxic effects induced by aminopyrine were studied in two inbred strains of mice, C57BL/6N and DBA/2N. Aminopyrine was given by subcutaneous injection at a dose of 200 mg/kg on day 7, 8 and 9 of gestation. In both strains, aminopyrine-induced malformations such as omphalocele, club foot and kinky tail were observed, but the incidence of malformations was significantly higher in C57BL/6N than in DBA/2N. Maternal plasma levels of aminopyrine and its metabolites were significantly higher in C57BL/6N, compared to DBA/2N. Further, reciprocal crosses between these two strains were used to clarify whether the maternal or fetal genotype is more important in aminopyrine-induced embryotoxicity. F1 hybrid embryos developing in C57BL/6N or DBA/2N mothers were as resistant as inbred DBA/2N. These results suggest that strain differences in susceptibility to aminopyrine may depend on fetal genotype rather than maternal factors.
在两种近交系小鼠C57BL/6N和DBA/2N中研究了氨基比林诱导的胚胎毒性作用。在妊娠第7、8和9天，以200mg/kg的剂量皮下注射氨基比林。在这两个品系中，均观察到氨基比林诱导的畸形，如脐膨出、马蹄内翻足和卷曲尾，但C57BL/6N品系中畸形的发生率显著高于DBA/2N品系。与DBA/2N相比，C57BL/6N母鼠血浆中氨基比林及其代谢产物的水平显著更高。此外，利用这两个品系之间的正反交来阐明在氨基比林诱导的胚胎毒性中，母本或胎儿基因型哪个更重要。在C57BL/6N或DBA/2N母体内发育的F1杂交胚胎与近交系DBA/2N胚胎一样具有抗性。这些结果表明，对氨基比林易感性的品系差异可能取决于胎儿基因型而非母本因素。
