家兎顎下腺に対する制癌剤の影響に関する研究 : Bleomycin および Mitomycin C と Vitamin C との併用

抄録

Chemotherapy for oral cancer, used alone or in combination with surgical therapy and radiation therapy appropriately, is no doubt a very important treatment method for prevention of local recurrence and distal metastasis, etc. Although many anticancer agents used today clinically have rather strong side effects, their administration for an extended period and in a large quantity is desirable from the standpoint of treatment. In anticipation of minimizing side effects and increasing anticancer effects, attempts are made to combine non-anticancer agents clinicaly such as vitamins and alkaloid. Of these non-anticancer agents, vitamin C (VC) is one of agents expected to restrain proliferation of tumors and to have immunological effect. It is used in combined administration with an anticancer agent and reported to increase anti-tumor effect clinically. Although the combined use of VC increases anti-cancer effect, cytocidal effect on normal cells and tissues also is expected from its use. It is therefore necessary to determine its cytocidal effect on the tissue of the oral cavity. The effect of the combined use of VC with Bleomycin (BLM) and Mitomycin C (MMC), most frequently used chemotherapeutic agents for oral cancer, on the submandibular gland of domestic rabbits was investigated histopathologically from the view point of side effects in the oral cavity region. The results were as follows : 1. The dosage of VC which did not affect the submandibular gland was 60 mg/kg/day. This dosage of VC was used in the combined administration of BLM and MMC thereafter. The dosage of anticancer agents were BLM (2.5mg/kg/day) and MMC (0.3mg/kg/day). 2. At the terminal portion of the submandibular gland, BLM-VC and MMC-VC combined administration cases, as compared with independent administration cases of BLM and MMC, showed marked findings such as atrophy of cytoplasm, pyknosis and deformation of nucleus, and even destruction of acinous cells (A and B cells). Along with these regressive changes, considerable decrease was observed in fine granules of A cells, PAS positive substance, and A・M stainable substance. 3. At the epithelial cells of duct constituting the intercalated duct and striated duct, both BLM-VC and MMC-VC administration cases, as compared with independent administration cases of BLM and MMC, markedly showed regressive changes such as atrophy of cytoplasm, pyknosis and deformation of nucleus. The surrounding capillary vessels showed stagnation, hyperemia, and dilation. 4. At the excretory duct in BLM-VC and MMC-VC combined administration cases, as compared with that in independent administration cases of BLM and MMC, the regressive changes in cytoplasm and nucleus of the epithelial cells were slight. 5. The foregoing regressive changes in acinous cells and epithelial cells appeared first in the peripheral part of the gland, gradually extended to the mid-gland, and intensi-fied. In the 15-dose cases, regressive changes were observed markedly in the whole gland. 6. The agents BLM and MMC both showed more marked regressive changes as their effects of combined use with VC than their independent administration. However, no apparent histologic changes specific to each agent were found. 7. On the basis of the foregoing experimental results, BLM and MMC not only showed morphological changes but also affected functions such as synthesis, accumulation, and excretion of secretory substances. The combined use of VC was though to aid and promote these regressive changes and reduction in functions further.