Effects of L-histidinol on the susceptibility of P815 mastocytoma cells to selected anticancer drugs in vitro and in DBA/2J mice.
The effects of L-histidinol on the susceptibility of the transplantable murine mast-cell neoplasm P815 mastocytoma to selected anticancer drugs have been evaluated on cells growing in culture and in syngeneic DBA/2J mice. Combinations of L-histidinol and anticancer drugs of either phase specificity [cytarabine (ara-C) and vinblastine sulfate] or cycle specificity [5-fluorouracil (FUra) and methotrexate] had diverse effects on cultured mastocytoma cells as scored by clonogenic cell survival assays. Flow cytometric analysis of randomly proliferating P815 mastocytoma cells revealed that although exposure to L-histidinol did not preclude cells from traversing the cell cycle, the analogue nonetheless conferred a dose-dependent and apparently nonspecific delay of cell cycle transit. DBA/2J mice bearing intraperitoneal P815 mastocytoma cells were used to evaluate the in vivo efficacy of L-histidinol-ara-C and of L-histidinol-FUra combinations. Quantitative cell survival assays of murine bone marrow cells and of clonogenic tumor cells obtained from treated animals demonstrated that L-histidinol eliminated the bone marrow toxicity otherwise attending the use of the drugs ara-C and FUra. Simultaneously, the inclusion of L-histidinol provided a statistically significant increase in the capacity of these two anticancer drugs to eradicate intraperitoneal mastocytoma cells.
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001853:Bone Marrow / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival; D003561:Cytarabine / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D005472:Fluorouracil / Q000008:administration & dosage; D006641:Histidinol / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D012515:Mast-Cell Sarcoma / Q000188:drug therapy*; D051379:Mice; D008811:Mice, Inbred DBA; D014411:Neoplastic Stem Cells / Q000187:drug effects; D010534:Peritoneal Neoplasms / Q000188:drug therapy
D000970:Antineoplastic Agents; D007093:Imidazoles; D003561:Cytarabine; D006641:Histidinol; D005472:Fluorouracil