This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Stolfi, R. L. Articles by Martin, D. S. Search for Related Content PubMed PubMed Citation Articles by Stolfi, R. L. Articles by Martin, D. S.

Failure of L-Histidinol to Improve the Therapeutic Efficiency of 5-Fluorouracil against Murine Breast Tumors¹

Department of Surgery-Research, Catholic Medical Center, Woodhaven, New York 11421

It has been reported that L-histidinol, a structural analogue of the essential amino acid L-histidine, can transiently inhibit proliferative cycling in cells with normal phenotype while allowing continued cell cycle transit in tumor cells. 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. Because of the potential clinical significance of this approach to reduce chemotherapy-associated host toxicity, we evaluated the L-histidinol-FUra combination in a nonlenkemic, solid murine tumor model, the BALB/c x DBA/8 F₁ (hereafter called CD8F₁) breast tumor. The results of these studies indicate that the administration of L-histidinol can protect the CD8F₁ mouse from FUra-associated leukopenia, body weight loss, and ultimately, from mortality. 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.

¹ This work was supported by National Cancer Institute Grant PO1-CA25842 and in part by the Chemotherapy Foundation of New York.

² To whom requests for reprints should be addressed, at The Catholic Medical Center of Brooklyn and Queens, 89-15 Woodhaven Boulevard, Woodhaven, NY 11421.

Received 4/14/86. Revised 8/18/86. Accepted 9/19/86.

This article has been cited by other articles:

				P. Klein and F. M. Muggia Cytoprotection: Shelter from the Storm Oncologist, April 1, 1999; 4(2): 112 - 121. [Full Text]