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Journal of Cell Science, Vol 92, Issue 1 37-49, Copyright © 1989 by Company of Biologists

JOURNAL ARTICLES

Methotrexate-induced morphological changes mimic those seen after heat shock

DA Jackson, CK Pearson, DC Fraser, KM Prise and SY Wong
Sir William Dunn School of Pathology, University of Oxford, UK.

The survival of cells cultured in medium containing the chemotherapeutic drug methotrexate (MTX) is related directly to drug concentration. Changes in DNA resulting from a severe imbalance in the cells' nucleotide pools are thought to account for this cytotoxicity. We have attempted to clarify the gross biochemical changes that might lead to cell death. DNA strand breaks occur in cells treated with high concentrations of MTX but it is not clear that these are sufficient to account for cytotoxicity at lower doses. We observed dramatic changes in cytoskeletal morphology. Gross reorganization of the cytoskeleton is shown by immunolabelling but is high-lighted dramatically when cells are lysed to leave 'nucleoids'. The nature of the changes seen in MTX-treated cells is characteristic of the cells' general stress response, seen originally following heat shock. This study shows that other factors, such as changes in cytoskeletal function, must be considered together with any contribution from DNA damage, in order to account for the lethal effects of MTX.




© The Company of Biologists Ltd 1989