DePass L R, Weaver E V
J Toxicol Environ Health. 1982 Aug;10(2):297-305. doi: 10.1080/15287398209530252.
The Fischer 344 rat is being used increasingly in toxicology studies. There have been few reports in which rats of this strain were used in teratology and reproduction studies, but comparison of teratologic data with other toxic and points and kinetic information would be greatly facilitated by using the same strain. Therefore, the embryotoxic effects of two positive teratogens, aspirin and hydroxyurea, were compared in Fischer rats and in the commonly used Wistar rats. Aspirin was administered in single oral doses of 500 and 625 mg/kg on d 10; hydroxyurea was injected ip at 500 mg/kg on d 11. Dams were sacrificed on d 20 and fetuses examined for skeletal and visceral defects. Male and female fetal weights and lengths were significantly reduced in treated groups in both strains. Both teratogens caused a significant increase in resorptions in Wistar and Fischer rats. A wide variety of skeletal alterations were induced by both teratogens in both strains. These included extra ribs, fused or missing ribs, extra thoracic and lumbar vertebrae, split vertebral centra, and missing vertebrae. Only a small number of Fischer fetuses exhibited visceral malformations such as hydrocephaly and cleft palate. The frequency of soft-tissue malformations, including cleft palate and severe cardiac anomalies, was much higher in Wistar fetuses.
Fischer 344大鼠在毒理学研究中的应用越来越广泛。关于使用该品系大鼠进行致畸学和生殖研究的报道较少，但使用同一品系将极大地促进致畸学数据与其他毒性数据、毒代动力学信息的比较。因此，在Fischer大鼠和常用的Wistar大鼠中比较了两种阳性致畸剂阿司匹林和羟基脲的胚胎毒性作用。阿司匹林在妊娠第10天以500和625mg/kg的单次口服剂量给药；羟基脲在妊娠第11天以500mg/kg的剂量腹腔注射。在第20天处死母鼠，并检查胎儿的骨骼和内脏缺陷。在两个品系的处理组中，雄性和雌性胎儿的体重和体长均显著降低。两种致畸剂均导致Wistar和Fischer大鼠的吸收显著增加。两种致畸剂在两个品系中均诱导了多种骨骼改变。这些改变包括额外的肋骨、融合或缺失的肋骨、额外的胸椎和腰椎、椎体裂开以及椎体缺失。只有少数Fischer胎儿出现脑积水和腭裂等内脏畸形。在Wistar胎儿中，包括腭裂和严重心脏异常在内的软组织畸形发生率要高得多。
