e-7010 and Body-Weight

E7010 (N-[2-[(4-hydroxyphenyl)amino]-3-pyridinyl]-4-methoxybenzenesulfonamide), a sulfonamide antitumor agent that inhibits tubulin polymerization, was orally administered to male Slc:SD rats at doses of 50 and 75 mg/kg once a day for 2 weeks. E7010 at a dose of 75 mg/kg induced severe testicular lesions characterized by marked decrease and/or loss of seminiferous epithelial cells, which sometimes resulted in tubules with only Sertoli cells. In the 50 mg/kg group, alteration of germ cells was evident at various stages of spermatogenesis, and apoptotic figures of meiotic spermatocytes at stage XIV were frequently observed. Single dose treatment of 50 mg/kg was also performed and was revealed a decrease of round spermatids in stage VII at necropsy after 1 week. Thus the target cells were considered to be meiotic spermatocytes at stage XIV. The present study indicates that 2-weeks repeated dosing is sufficient to detect the testicular toxicity of E7010.

Topics: Administration, Oral; Aminophenols; Animals; Antineoplastic Agents; Apoptosis; Body Weight; Dose-Response Relationship, Drug; Epididymis; In Situ Nick-End Labeling; Male; Organ Size; Polymers; Random Allocation; Rats; Rats, Sprague-Dawley; Seminiferous Epithelium; Spermatogenesis; Sulfonamides; Testis; Time Factors; Toxicity Tests; Tubulin