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.
Warrington
R C
RC
Department of Biochemistry, University of Saskatchewan, Saskatoon, Canada.
Fang
W D
WD
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001761:Bleomycin / Q000008:administration & dosage; D002330:Carmustine / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D004347:Drug Interactions; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006639:Histidine / Q000494:pharmacology; D006641:Histidinol / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary*; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary*; D008727:Methotrexate / Q000008:administration & dosage; D051379:Mice; D008810:Mice, Inbred C57BL
D003561:Cytarabine; D001761:Bleomycin; D006639:Histidine; D006641:Histidinol; D004317:Doxorubicin; D002945:Cisplatin; D005472:Fluorouracil; D002330:Carmustine; D008727:Methotrexate