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Modulation of antifolate cytotoxicity by metabolites from dying cells in a lymphocyte clonal assay
- Source :
- British Journal of Cancer
- Publication Year :
- 1988
- Publisher :
- Nature Publishing Group, 1988.
-
Abstract
- A lymphocyte clonal assay developed to quantitate in vivo somatic cell mutations at the hypoxanthine-guanine phosphoribosyltransferase locus was modified in order to study resistance to methotrexate. Even though nucleoside-free culture conditions were used methotrexate was not lethal to lymphocytes plated into micro-wells at greater than 10(2) cells/well. HPLC analysis of supernatants from wells plated initially with 10(4) cells/well in 100 microM methotrexate revealed the presence of micro-molar levels of hypoxanthine and thymidine by the 5th and 8th day of culture respectively. When lymphocytes were plated at less than or equal to 10(2) cells/well in nucleoside free medium, methotrexate was cytotoxic and micro-molar levels of thymidine together with hypoxanthine protected lymphocytes cultured under these conditions from toxicity. Modulation of nucleic acid antimetabolite cytotoxicity by nucleosides and bases has been recognised for some years. Nucleoside free culture conditions have been advocated for studying cellular sensitivity to antifolates to avoid such interfering factors. However our results indicate that metabolites from dying or damaged cells can prevent methotrexate cytotoxicity, further complicating the development of a suitable clonogenic assay for investigating antifolate sensitivity.
- Subjects :
- Cancer Research
Lymphocyte
Drug Resistance
Biology
Colony-Forming Units Assay
chemistry.chemical_compound
medicine
Cytotoxic T cell
Humans
Lymphocytes
Cytotoxicity
Clonogenic assay
Hypoxanthine
Cells, Cultured
Chromatography, High Pressure Liquid
Molecular biology
medicine.anatomical_structure
Methotrexate
Oncology
chemistry
Hypoxanthines
Antifolate
Thymidine
Cell Division
medicine.drug
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 15321827 and 00070920
- Volume :
- 57
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- British Journal of Cancer
- Accession number :
- edsair.doi.dedup.....5e449965bb5c3f114ebfe023f335e19b