Possible Interaction: Fluorouracil and Histidine

“In contrast, L-histidinol prevented the weight loss, death and bone marrow damage otherwise resulting from identical doses of FUra.”

“ L-Histidinol enhanced the ability of bis-chloroethylnitrosourea, 5-fluorouracil , and 1-beta-D-arabinofuranosulcytosine to reduce the number of lung foci.”

“ L-Histidinol , a structural analogue of histidine, which transiently inhibits proliferation, can protect cells from the toxic effects of proliferation-dependent chemotherapeutic agents such as 5-fluorouracil (FUra).”

“Since the major mechanism of action in the CD8F1 breast tumor system is the … of FUra into RNA, the reduction in toxicity and antitumor activity observed when L-histidinol is combined with FUra is consistent with the observed reduction in tumor and bone marrow RNA containing incorporated FUra residues.”

“We conclude that L-histidinol reduces FUra toxicity by reducing FUra incorporation into RNA.”

“ L-Histidinol , an analogue of the amino acid L-histidine, has been reported to be able to increase the specificity of 5-fluorouracil ( FUra ), through both protection of normal tissues at risk and potentiation of leukemic cell killing.”

“However, in contrast to results reported in the L1210 leukemic system, L-histidinol also reduced the cytotoxic activity of FUra against CD8F1 breast tumors.”

“Therefore, although the dose of FUra that could be administered with safety was higher in mice receiving L-histidinol , the therapeutic results of the combination of FUra and L-histidinol were not superior to those obtained with FUra alone at a lower dose.”

“Thus, in the presence of L-histidinol , the toxicity of a proliferation-dependent drug such as 5-fluorouracil (FUra) was found to be reduced in normal tissue cells of the DBA/2J mouse, but not in L1210 leukemia cells in the same mouse.”

“Thus, L-histidinol diminishes the myelocytoxicity otherwise associated with the in vivo use of agents such as cytosine arabinoside and 5-fluorouracil.”

“It was previously demonstrated that L-histidinol , a structural analogue of the essential amino acid L-histidine, improves the specificity of cytarabine (ara-C) and 5-fluorouracil (FUra) in DBA/2J mice bearing intraperitoneal L 1210 leukemia.”

“Thus L-histidinol mediates a substantial increase in the specificities of ara-C and FUra in mice bearing an established bone marrow leukemic condition.”

“ 5-FU increased the endogenous levels of arginine, histidine and aspartate in both lines.”