Effects of mitomycin C administered at various stages of pregnancy upon mouse fetuses.

Many cancer therapeutic agents have been used for experimental and clinical purposes. It has been established that generally such agents are toxic to embryos with highly mitotic activities as well as other rapidly growing or proliferating tissues. The teratogenicity of these agents has been shown in rodents (Reviewed by Nishimura, '64; Karnof sky, '65; Dagg, '66). Murphy et at. ('58) found that the effects of various alkylating .agents upon rat embryos were similar to each other, while some principal differences in teratogenic action existed between alkylating agents and antimetabolites. Mitomycin is an antibiotic isolated in Japan from a new actinomyces strain named streptomyces caespitosus discovered by Hata et al. ('56) and has strong activity against various microbes and malignant tumor cells. Among three kinds of mitomycin, mitomycin C introduced by W a k a k i et at. ('58) was found to be the most stable and the least toxic one and has been applied in clinical use. The mechanism of action of mitomycin C has been established to be the inhibition of biosynthesis of nucleic acids, especially of DNA. In a previous report, the author presented a comprehensive study on the effect of thio-TEPA, one of the potent antineoplastic alkylating agents, upon mouse embryos (T a n i m u r a, '68). The study to be reported here was designed to compare the effect of mitomycin C upon mouse embryos with the results obtained by the use of thio-TEPA.