Infused L-histidinol and cisplatin: schedule, specificity, and proliferation dependence

The dose and schedule requirements found for the combination of L-histidinol and 5-fluorouracil (5-FU) were concordant with those for the combination of L-histidinol and cisplatin. Furthermore, cisplatin-L-histidinol was active against colon 26 tumor, an adenocarcinoma that developed in a BALB/c female mouse and that has been grown as a solid tumor. The toxicity of cisplatin was prevented only when cisplatin was given before L-histidinol. Studies of L-histidinol and 5-FU had similar results. For (DBA/2 X BALB/c)F1 mice, 50 mg of L-histidinol per mouse was required for protection; for hematopoietic precursor cells, protection was dependent on the dose of L-histidinol. In contrast, both L1210 leukemia cells and colon 26 adenocarcinoma cells were more efficiently killed by combinations of L-histidinol and cisplatin. This effect depended on the doses of L-histidinol and cisplatin, a finding similar to the finding for hematopoietic precursor cells.