Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 17). Testicular toxicity of E7010, a sulfonamide tubulin polymerization inhibitor.
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.
Hayakawa
K
K
Drug Safety & Disposition Research Laboratories, Eisai Co., Ltd., 1 Takehaya, Kawashima-cho, Hashima-gun, Gifu 501-6195, Japan.
Tashiro
T
T
Sato
K
K
Katsurayama
T
T
Imai
T
T
Hosokawa
S
S
Sagami
F
F
D000284:Administration, Oral; D000627:Aminophenols / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004822:Epididymis / Q000187:drug effects / Q000473:pathology; D020287:In Situ Nick-End Labeling; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011108:Polymers; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012670:Seminiferous Epithelium / Q000187:drug effects / Q000473:pathology; D013091:Spermatogenesis / Q000187:drug effects; D013449:Sulfonamides / Q000008:administration & dosage / Q000633:toxicity*; D013737:Testis / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D018675:Toxicity Tests; D014404:Tubulin / Q000187:drug effects* / Q000378:metabolism; D000096926:Benzenesulfonamides
D000627:Aminophenols; D000970:Antineoplastic Agents; D011108:Polymers; D013449:Sulfonamides; D014404:Tubulin; C079199:E 7010; D000096926:Benzenesulfonamides