Improved treatment of disseminated B16f10 melanoma in mice with anticancer drugs in combination with L-histidinol

: An artificial hematogenous-metastasis model, in which B16f10 melanoma cells injected into the tail veins of C57/BL mice arrest in the lungs and proliferate as discrete pulmonary foci, was employed to examine effects of L-histidinol on the capacity of a number of conventional antineoplastic agents to manage disseminated disease. Treatment responses were evaluated by determining both the number of lung foci and/or by evaluating animal survival. L-Histidinol, on its own, was found to have a significant and dose-dependent capacity to reduce the number of lung foci and to extend survival of animals bearing disseminated B16f10 melanoma. L-Histidinol enhanced the ability of bis-chloroethylnitrosourea, 5-fluorouracil, and 1-beta-D-arabinofuranosulcytosine to reduce the number of lung foci. The latter combinations also gave marked improvements in survival, whether administered 1 or 7 days after the intravenous injection of tumor cells.