{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T17:07:58Z","timestamp":1767373678366},"reference-count":44,"publisher":"The Company of Biologists","issue":"1","license":[{"start":{"date-parts":[[1989,1,1]],"date-time":"1989-01-01T00:00:00Z","timestamp":599616000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1989,1,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>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\u2019 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 highlighted dramatically when cells are lysed to leave \u2018nucleoids\u2019. The nature of the changes seen in MTX-treated cells is characteristic of the cells\u2019 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.<\/jats:p>","DOI":"10.1242\/jcs.92.1.37","type":"journal-article","created":{"date-parts":[[2021,4,24]],"date-time":"2021-04-24T05:41:09Z","timestamp":1619242869000},"page":"37-49","source":"Crossref","is-referenced-by-count":4,"title":["Methotrexate-induced morphological changes mimic those seen after heat shock"],"prefix":"10.1242","volume":"92","author":[{"given":"Dean A.","family":"Jackson","sequence":"first","affiliation":[{"name":"University of Oxford, South Parks Road 1 Sir William Dunn School of Pathology , , Oxford OXI 3RE, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colin K.","family":"Pearson","sequence":"additional","affiliation":[{"name":"University of Aberdeen, Department of Biochemistry, Marischal College 2 , Aberdeen AB9 IAS, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas C.","family":"Fraser","sequence":"additional","affiliation":[{"name":"University of Aberdeen, Department of Biochemistry, Marischal College 2 , Aberdeen AB9 IAS, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin M.","family":"Prise","sequence":"additional","affiliation":[{"name":"University of Aberdeen, Department of Biochemistry, Marischal College 2 , Aberdeen AB9 IAS, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Su Y.","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Pathology, University Medical Buildings, Foresterhill 3 , Aberdeen AB9 2ZD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[1989,1,1]]},"reference":[{"key":"2023091603562352100_JOCES_92_1_37C1","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1002\/ijc.2910300215","article-title":"Monitoring the effects of anti-cancer drugs on L1210 cells by a mitochondrial probe, rhodanune-123","volume":"30","author":"Bernal","year":"1982","journal-title":"int. 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