博来霉素A_6对小鼠肺毒性的电子显微镜观察

An electron-microscopic study on pulmonary toxicity of bleomycin A_6 in mice

用电子显微镜观察比较博来霉素A_6和目前临床使用的博来霉素(复合物)对小鼠的肺毒性。博来霉素A_6和博来霉素分别以相当于1/40、1/20和1/10 LD_(50)剂量给小鼠ip 7d或10 d。病变表现为肺毛细血管的损伤,内皮细胞胞浆空泡、皂泡样变、网状化、伪足样突起、血小板粘着和微血栓形成等最为常见。博来霉素A_6引起的肺病变明显地较博来霉素为轻,提示博来霉素A_6有可能成为肺毒性较低的博来霉素类抗癌药物。

Bleomycin A6 is effective against a panel of transplantable tumors in mice.It is highly cytotoxic to several human cancer cell lines and exhibits remarkable growth inhibition on human liver cancer xenografts in nude mice.As well known,pulmonary toxicity is the most serious side-effect of bleomycin.In the present study,we compared the lung toxicity of bleomycin A6 with that of bleomycin in mice under the electron microscope.Both bleomycin A6 and bleomycin were administered intraperitoneally once daily for 10 d or 7 d at the dosage of 1/40,1/20 or 1/10 LD50,the changes in the endothelia of the alveolar capillaries included pseudopodium-like flaps,cytoplasm reticulation,large vacuole and foam-like changes,platelet adhesion and the formation of microthrombus.Capillaries with the above-mentioned changes were counted under the electron microscope.The results showed that the percentage of the injured capillaries elicited by bleomycin A6 was much lower than that by bleomycin,suggesting that bleomycin A6 may be a potential bleomycin-related drug with less pulmonary toxicity.