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Science 30 November 1979:
Vol. 206. no. 4422, pp. 1085 - 1087
DOI: 10.1126/science.493993
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Articles

Science, Vol 206, Issue 4422, 1085-1087
Copyright © 1979 by American Association for the Advancement of Science

articles

Differential competition with cytotoxic agents: an approach to selectivity in cancer chemotherapy

M Rabinowitz, Y Uehara, and DT Vistica

An approach to increasing the selectivity of cancer chemotherapeutic agents is presented in which noncytotoxic competitive substrates are used to discern the differences in structural requirements for transport of cytotoxic agents between tumor cells and a sensitive host tissue, the hematopoietic precursor cells of the bone marrow. Examples are given for two such systems, one responsible for the transport of nucleosides and another for the transport of amino acids. Cytidine is twice as effective in reducing the toxicity of showdomycin for murine bone marrow cells in culture as it is for murine L1210 leukemia cella. Conversely, homoleucine is twice as effective in reducing the toxicity of melphalan for L1210 cells as it is for bone marrow cells. These observations can serve as a basis for the development of bone marrow protective agents and for the design of cytotoxic agents that may be preferentially transported into tumor cells.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Effect of N-(4-Acetyl-1-piperazinyl)-p-fluorobenzamide Monohydrate (FK960), an Antidementia Drug with a Novel Mechanism of Action, on Regional Cerebral Blood Flow and Glucose Metabolism in Aged Rhesus Macaques Studied with Positron Emission Tomography.
A. Noda, H. Takamatsu, N. Matsuoka, S. Koyama, H. Tsukada, and S. Nishimura (2003)
J. Pharmacol. Exp. Ther. 306, 213-217
   Abstract »    Full Text »    PDF »
Effects of ({+/-})-4-{[2-(1-Methyl-2-pyrrolidinyl)ethyl]thio}phenol Hydrochloride (SIB-1553A), a Selective Ligand for Nicotinic Acetylcholine Receptors, in Tests of Visual Attention and Distractibility in Rats and Monkeys.
A. V. Terry Jr., V. B. Risbrough, J. J. Buccafusco, and F. Menzaghi (2002)
J. Pharmacol. Exp. Ther. 301, 284-292
   Abstract »    Full Text »    PDF »


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