Cyclophosphamide (Cytoxan, Endoxan), synthesized by Arnold, Bourseaux and Brock, is an anticancer agent with antitumor effects against a wide variety of human neoplasms, including Hodgkin´s disease, lymphosarcoma, Burkitt´s lymphoma and acute lymphoblactic leukemia. more recently, its immunosuppressive properties have been exploited successfully in the treatment of nonneoplastic diseases such as rheumatoid arthritis and lupus erythematosus. The cytotoxic and other effects of cyclophosphamide as alkylating agent are directly related to the alkylation of components of DNA, and the breakdown of cyclophosphamide into biologically active alkylating compounds takes place principally in the liver. Thus the author observed the ulltrastructural changes of cytoplasmic oganelles in the hepatic parenchymal cells in order to investigate the effect of cyclophosphamide on the normal rbbits.
Healthy normal rabbits, weighing 1500 gram each, were divided into the control and cyclophosphamide treatment group. Cyclophosphamide in distilled water was given intravenously through ear vein in a dose of 40 mg per kg of body weight for nine days. Control animals were injected intravenously with isotonic saline solution. The animals were killed on the 9th day of cyclophosphamide treatment. Liver specimen of 1mm³size were prefixed in the 2% glutaraldehyde-2.5% paraformaldehyde phosphate solution(pH 7.2) and postfixed in the 1% osmic acid. The ultrathin sections (600-800 A?), double-stained with uranyl acetate and lead cirate, were observed with JEM 100 B electron microscopy.
The results which were observed in the hepatic parenchymal cells from the cyclophosphamide-treated rabbits were as follows;
1) The dilatation of the cisternae of rough endoplasmic reticulum associated with deatchment of membrane bound-ribosomes and marked depletion of polysome in cytoplasm were observed.
2) There was proliferation of smooth endoplasmic reticulum in hepatocytes of midzonal area of the lobules associated with depletion of glycogen particles.
3) A few lysosomes and pronounced formation of autophagic vacuoles as well as multivesicular body were also noted. Through the experiment, there were no alterations in the morphology of the nuclei or nucleoli.
Consequently, itis suggested that cyclophosphamide would induce the degenerative changes of cytoplasmic organelles of the hepatic parenchymal cells on prolonged treatment in rabbits.
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