mitolactol and Body-Weight

The efficacy and modes of action of dibromodulcitol (DBD) and cisplatin (CDDP) were studied in several model systems. Combination treatments produced a longer survival time in mice bearing P388 solid lymphomas than either of the drugs alone. In the human metastatic melanoma HT-168 xenograft model the combined application of DBD and CDDP was also very effective, inducing a reduction in the number and volume of metastatic nodules. For V79 spheroids, DBD was mainly cytotoxic against the internal, quiescent cells, whereas cisplatin primarily killed cells in the proliferating, external regions of the spheroids. When combined, the drugs appeared to act synergistically throughout the spheroids. Studies on plasmid DNA showed that CDDP primarily generates cross-links, whereas single-strand breaks were dominant after DBD treatment. Upon using an assay for cleavage by restriction nuclease, antagonistic action of DBD and CDDP in combination may occur, nevertheless more strand breaks were always observed in these samples. These results suggest that the efficacy of combined DBD and CDDP is in part a result of 'spatial cooperation' by the drugs (i.e. affecting different cells) and in part the result of DNA damage produced by the combination treatments.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Body Weight; Cisplatin; DNA Damage; DNA, Neoplasm; Drug Screening Assays, Antitumor; Drug Synergism; Leukemia P388; Male; Melanoma; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Inbred DBA; Mitolactol; Neoplasm Metastasis; Neoplasm Transplantation; Tumor Cells, Cultured

Mitolactol (Dibromodulcitol "DBD"; RlobromolR) an alkylating agent was applied in a clinical series of twenty advanced or relapsing cases of malignant tumors of the orofacial region and the larynx. It was administered orally in a mean total dose of 127 mg/kg/30 days. In 45% of the patients the treatment resulted in a diminution of tumors by more than 50%, with remission lasting 1-4 months. 30% of the patients responded by a retreat of the tumor volume smaller than 50%, while no therapeutic effect was noted in 25% of the patients, or the objective finding proved to be worse. Subsequent radiotherapy improved the results, and remissions which followed combined chemo-radiotherapy were prolonged up to 9 months. The effect of DBD treatment proved better in orofacial than in laryngeal carcinoma.

Topics: Adult; Aged; Body Weight; Drug Evaluation; Facial Neoplasms; Female; Hemorrhage; Humans; Laryngeal Diseases; Laryngeal Neoplasms; Male; Middle Aged; Mitolactol; Mouth Neoplasms; Recurrence; Remission, Spontaneous

Disturbances of osseal growth were observed in young mice with their lymphoid system affected by antihymocyte serum or mitolactol (dibromodulcitol) treatment. These bone changes were similar to those observed in germ-free and neonatally thymectomized mice as well as in mice suffering from a graft vs. host reaction. Their severity was in direct correlation with the disturbance of the thymus dependent lymphoid system. Not only immunological adaptation but also normal bone growth appears to require an intact thymus and thymus dependent lymphoid system.

Topics: Animals; Antilymphocyte Serum; Body Weight; Bone Development; Epiphyses; Femur; Histological Techniques; Injections, Intraperitoneal; Leukocyte Count; Mice; Mice, Inbred C3H; Mitolactol; Osteogenesis; Radiography; T-Lymphocytes; Thymus Gland