[Quantitative evaluation for murine oocyte toxicity following intraperitoneal treatment with chemotherapeutic agents].
The ovarian toxicity induced with 12 oncostatics was evaluated using syngeneic mice, 6-week-old C57BL/6. Each drug diluted with saline to 0.2ml was intraperitoneally infused twice at 6 and 7 weeks old. Mice were sacrificed 2 weeks after the second treatment, the ovaries removed and fixed for serial sectioning, and the small oocytes of Pedersen and Peters counted. Small oocytes were destroyed in a dose-dependent fashion, and ED50, an effective dose of which produced 50% destruction of small oocytes in each mice group, was significantly divided into 4 groups of statistical difference (F = 5.77, p less than 0.0213). The smallest dose of ED50 (mg/mouse) (the strongest in oocyte toxicity): Actinomycin D 0.0064, doxorubicin 0.0184, peplomycin 0.021; the second: Bleomycin 0.107, mitomycin 0.0707, CDDP 0.120; the third: Cyclophosphamide 0.427; and the largest (the weakest): Ifosphamide 3.01, 5FU 6.17, etoposide 6.11, methotrexate 2.0 much less than, vinblastine 0.1 much less than. The most toxic included those which could attack not only DNA, but also RNA biosynthesis and the least included those which could have an effect on enzymes or proteins with no direct action on DNA. The ratio of ED50 to HUD, the single usual dose for human cancer chemotherapy, were smallest for doxorubicin (2.23), cyclophosphamide (2.59) and CDDP (5.19). Although these three are very useful oncostatics for ovarian cancer, they might have serious potential toxicity for human ovarian oocytes.
Takizawa
K
K
Department of Obstetrics and Gynecology, Tokyo Women's Medical College.
Yokoo
I
I
Shima
Y
Y
Inou
Y
Y
Sato
M
M
Iguchi
T
T
Takeda
Y
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000633:toxicity*; D002452:Cell Count / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D007263:Infusions, Parenteral; D051379:Mice; D008810:Mice, Inbred C57BL; D009865:Oocytes / Q000166:cytology / Q000187:drug effects*; D015430:Weight Gain / Q000187:drug effects
D000970:Antineoplastic Agents