Publication Date:
1979-11-30
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rabinowitz, M -- Uehara, Y -- Vistica, D T -- New York, N.Y. -- Science. 1979 Nov 30;206(4422):1085-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/493993" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Antibiotics, Antineoplastic/*metabolism
;
Biological Transport
;
Bone Marrow/drug effects
;
Leukemia L1210/drug therapy
;
Melphalan/metabolism/therapeutic use
;
Mice
;
Neoplasms/*drug therapy
;
Showdomycin/*metabolism/therapeutic use
;
Structure-Activity Relationship
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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