Experimental Model for Combination Chemotherapy with Metronidazole Using Human Uterine Cervical Carcinomas Transplanted into Nude Mice

Human uterine cervical carcinomas (Yumoto strain) and HeLa cell tumors were transplanted into nude mice, and their transplantable strains were established. The fundamental histological features of these tumors were analyzed according to their histological construction and cytological maturation. The effect of administered drugs was examined morphologically. The Yumoto strain is a well-differentiated epidermoid-type carcinoma consisting of regularly arranged basal-type, parabasal-type, and keratinizing-type cells. The HeLa cell tumor is made up of solid medullary carcinoma cell nests in which trabecular arrangements begin to appear around the medullary areas after the third passage. This feature is maintained up to the 17th generation. The basal layer-type cancer cells of the Yumoto strain as well as trabecularly arranged cancer cells in the HeLa cell tumor were selectively influenced by administration of bleomycin and/or mitomycin and showed considerable degeneration or complete disappearance. On the contrary, metronidazole (a drug for vaginal trichomoniasis; Flagyl) displayed a cytotoxic effect on the parabasal-type and/or more mature cancer cells of the Yumoto strain as well as on the solid medullary area of the HeLa cell tumor. This result may indicate a selective affinity of drugs for malignant cells according to their histological construction, and it is conceivable that these types of carcinoma can be affected by combination administration of metronidazole and oncostatic chemicals such as bleomycin and mitomycin. This speculation was realized in this experimental animal research.