Toxicologic and Therapeutic Examinations with Ftorafur in Different Mouse Strains
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Ftorafur, a derivative of the antimetabolite 5-Fluorouracil, was tested for its toxicologic and therapeutic effectivity in the mouse strains XVII/Berlin, F1 (NMRI X DBA/2), Balb/c -- +/+, Balb/c -- nu/+, Balb/c -- nu/nu. The LD values were similar in all strains tested, with a somewhat higher sensibility of the homozygous nude mice. In each case lethality was higher in male than in female animals. This tendency was confirmed by the always more pronounced leukopenia in male versus female mice after high doses of Ftorafur. Thrombocytes, hemoglobin and hematocrit were not influenced by Ftorafur treatment, whereas marked reticulopenias were observed. While in the L1210 model significant ILS values without distinct leukopenias were obtained, no convincing effectivity could be demonstrated in any of the other tumor models. The results confirm that it is possible to compare phenotypical normal with nude mice both with regard to dosage levels and therapeutic activity.
A strategy for primary high throughput cytotoxicity screening in pharmaceutical toxicology.
Bugelski P, Atif U, Molton S, Toeg I, Lord P, Morgan D Pharm Res. 2001; 17(10):1265-72.
PMID: 11145233 DOI: 10.1023/a:1026495503939.