title: Direct effects of CPT-11 and SN38 on ovarian granulosa cells.
abstract: This study aimed to clarify the mechanism by which apoptosis and Fas ligand (FasL) expression are induced in the ovarian granulosa cells of mice injected with irinotecan HCl (CPT-11). To this end, the direct effects of CPT-11 and its active metabolite, SN38, on granulosa cells were investigated. Normal ovarian tissue fragments obtained from 8-week-old female MCH mice were cultured in vitro with CPT-11 or SN38 and paraffin-embedded. After sectioning, the ovarian fragments were analyzed by TUNEL staining to detect apoptotic cells and by immunohistochemistry with an anti-FasL antibody to detect FasL expression. The results revealed no increase in TUNEL-positive granulosa cells in the ovarian tissue fragments cultured with CPT-11 or SN38. Furthermore, CPT-11 and SN38 did not induce FasL expression in the ovarian fragments. In conclusion, apoptosis and FasL expression induced in the ovarian granulosa cells of mice injected with CPT-11 is not caused by direct stimulation with CPT-11 or SN38. Therefore, systemic CPT-11 administration appears to induce apoptosis and FasL expression in granulosa cells via currently unknown endogenous FasL-inducing factors or by active metabolites of CPT-11 other than SN38.
authors.affiliation: Department of Obstetrics and Gynecology, Wakayama Medical University, Wakayama 641-0012, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Utsunomiya
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Tanaka
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Utsunomiya
authors.forename: Naohiko
authors.initials: N
authors.lastname: Umesaki