Comparison of teratogenic effects of aspirin and hydroxyurea in the Fischer 344 and Wistar strains

Abstract

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.

Management of Sickle Cell Disease: Recent Advances and Controversies

“…First, the frequent blood tests required for toxicity prevention affect the quality of the patients' lives and furthermore it is possible that an occasional patient may still develop serious myelotoxicity despite these measures. Second, most young adults need to consider the mutagenicity ( Ziegler‐Skylakakis et al , 1985 ) and potential teratogenicity ( DePass & Weaver, 1982) of hydroxyurea so that this treatment may affect their decision to have children. Third, there is the potential oncogenicity of anti‐neoplastic drugs so that long‐term hydroxyurea treatment could predispose to cancer or leukaemia.…”

Anophthalmia in Litters of Female Rats Treated with the Food-Derived Carcinogen, 2-Amino-1-Methyl-6-Phenylimidazo[4,5-b]Pyridine

“…In both trials, congenital malformations, anophthalmia ( Fig. 2A) (20) and 0.05-0.16% in the Wistar strain (11,16), and such abnormalities are very rare in the Fischer 344 strain (2,10,30). In light of these reports, the 18.4% incidence observed for 200 ppm PhIP-treated rats can be considered to be extremely high, although to our knowledge, no data for Fischer 344 rats have been published.…”

Developmental Toxicity of Aspirin Prenatally Given to Rats: Assessment in Sic: Wistar‐KY Rats

“…DePass and Weaver (1982) also indicated that there were some differences in effects of aspirin between Fisher 344 and Wistar strains. DePass and Weaver (1982) also reported that Wistar rats treated with 500 mg/kg aspirin on day 10 of gestation showed a lower fetal weight, an increased rate of resorptions and some malformations, especially a higher incidence of skeletal defects. A double staining method revealed a higher rate of variant of cartilages such as the fusion of costal cartilages in the aspirintreated groups, which could be missed by the conventional skeletal staining.…”