Document Detail


Factors that influence the penetration of methotrexate through solid tissue.
MedLine Citation:
PMID:  11149410     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Limited penetration of anticancer drugs through tumour tissue is an important factor that may limit therapeutic effects against solid tumours. Here we report studies of the penetration of radiolabelled methotrexate through multicellular layers (MCL) of murine EMT-6 and human MCF-7 cells grown on semiporous teflon membranes. The penetration of methotrexate was only about 25% of that through the teflon membrane alone after 6 hr. This was true for all methotrexate concentrations examined from 10 microM to 3 mM. The presence of folic acid at concentrations above 0.1 mM and of acidic conditions decreased the uptake of methotrexate into single cells and enhanced tissue penetration. Hypoxic conditions and the presence of folinic acid (leucovorin) had no effect on penetration or uptake of methotrexate. Our data provide evidence that tissue penetration of methotrexate is through the extracellular space, that its distribution in solid tissue may be limited and that it may be possible to improve its tissue penetration.
Authors:
D S Cowan; I F Tannock
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  91     ISSN:  0020-7136     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2001 Jan 
Date Detail:
Created Date:  2001-01-08     Completed Date:  2001-01-25     Revised Date:  2007-07-24    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  120-5     Citation Subset:  IM    
Affiliation:
Department of Medicine, Ontario Cancer Institute and University of Toronto, Ontario, Canada.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anoxia
Antimetabolites, Antineoplastic / pharmacokinetics*
Breast Neoplasms / drug therapy
Cell Culture Techniques
Cell Survival / drug effects
Dose-Response Relationship, Drug
Female
Folic Acid / pharmacology
Humans
Hydrogen-Ion Concentration
Leucovorin / pharmacology
Mammary Neoplasms, Animal / drug therapy
Methotrexate / pharmacokinetics*
Mice
Polytetrafluoroethylene
Time Factors
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
0/Antimetabolites, Antineoplastic; 58-05-9/Leucovorin; 59-05-2/Methotrexate; 59-30-3/Folic Acid; 9002-84-0/Polytetrafluoroethylene

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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