{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:39:35Z","timestamp":1786977575295,"version":"build-2736575974"},"reference-count":30,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2004,2,26]],"date-time":"2004-02-26T00:00:00Z","timestamp":1077753600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2004,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>5\u2010fluorouracil (5\u2010FU) is a widely used anticancer drug. One of the adverse effects of this drug is selective cerebral white matter injury, but to the authors' knowledge its mechanism has not been well documented. The current study was performed to investigate the mechanism of cerebral white matter injury caused by 5\u2010FU and to develop the intervention to attenuate its injury in vitro.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Mixed oligodendrocyte\/astrocyte cells were dissociated from specimens taken from approximately 2\u2010day\u2010old postnatal mouse cortex and cultured for 3\u20134 weeks. The culture cells were exposed to 5\u2010FU, cycloheximide, emetine, Z\u2010VAD\u2010fmk, 2,3\u2010dihydroxy\u20106\u2010nitro\u20107\u2010sulfamoyl\u2010benzo(F)\u2010quinoxaline (NBQX), Trolox, and epigallocatechin gallate. Oligodendrocyte cell death was assessed by counting the number of viable galactocerebroside\u2010positive cells per \u00d7 100 field.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Mixed oligodendrocyte\/astrocyte culture cells that were exposed to 5\u2010FU (at doses of 10 \u03bcM, 30 \u03bcM, and 100 \u03bcM) for 24 hours ensued concentration\u2010dependent oligodendrocyte death. The majority of oligodendrocytes, but few astrocytes, were injured by 100 \u03bcM 5\u2010FU. Trolox, a vitamin E analog antioxidant, as well as cycloheximide (a protein synthesis inhibitor) and Z\u2010VAD\u2010fmk (a caspase inhibitor), significantly attenuated the 5\u2010FU\u2013induced oligodendrocyte death. However, NBQX, an alpha\u2010amino\u20102,3\u2010dihydro\u20105\u2010methyl\u20103\u2010oxo\u20104\u2010isoxazolepropionic acid (AMPA) receptor antagonist, did not appear to effect the 5\u2010FU\u2013induced oligodentrocyte death.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>The findings of the current study suggested that 5\u2010FU led to oligodendrocyte death rather than astrocyte death by way of the apoptotic process, whereas antioxidants may prevent the 5\u2010FU\u2013induced oligodendrocyte cell death in vitro. Cancer 2004;100:1484\u201390. \u00a9 2004 American Cancer Society.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cncr.20114","type":"journal-article","created":{"date-parts":[[2004,3,23]],"date-time":"2004-03-23T08:40:57Z","timestamp":1080031257000},"page":"1484-1490","source":"Crossref","is-referenced-by-count":10,"title":["5\u2010fluorouracil\u2010induced oligodendrocyte death and inhibitory effect of cycloheximide, trolox, and Z\u2010VAD\u2010FMK in murine cortical culture"],"prefix":"10.1002","volume":"100","author":[{"given":"Ki\u2010Hyun","family":"Cho","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung\u2010Min","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byeong\u2010Chae","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung\u2010Han","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man\u2010Seok","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myeong\u2010Kyu","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong\u2010Keun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2004,2,26]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410310306"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/00006123-199412000-00019"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.3346\/jkms.2001.16.3.328"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0733-8619(18)30259-7"},{"key":"e_1_2_5_6_2","first-page":"125","article-title":"Neurological complications of antineoplastic therapy","volume":"100","author":"Shapiro WR","year":"1984","journal-title":"Acta Neurol Scand"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9394(77)90904-7"},{"key":"e_1_2_5_8_2","first-page":"77","article-title":"Acute cerebellar syndrome after treatment with 5\u2010fluorouracil","volume":"83","author":"Barbieux C","year":"1996","journal-title":"Bull Cancer."},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00662639"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004010050482"},{"key":"e_1_2_5_11_2","first-page":"19","article-title":"Activation of caspase\u20103 in renal cell carcinoma cells by anthracyclines or 5\u2010fluorouracil","volume":"19","author":"Wu XX","year":"2001","journal-title":"Int J Oncol."},{"key":"e_1_2_5_12_2","first-page":"1027","article-title":"Apoptosis of human primary and metastatic colon adenocarcinoma cell lines in vitro induced by 5\u2010fluorouracil, verapamil, and hyperthermia","volume":"14","author":"Shchepotin IB","year":"1994","journal-title":"Anticancer Res."},{"key":"e_1_2_5_13_2","first-page":"1489","article-title":"Apoptosis in normal tissues induced by 5\u2010fluorouracil: comparison between bolus injection and prolonged infusion","volume":"14","author":"Sakaguchi Y","year":"1994","journal-title":"Anticancer Res."},{"key":"e_1_2_5_14_2","first-page":"3117","article-title":"Involvement of caspases in 5\u2010FU induced apoptosis in an oral cancer cell line","volume":"20","author":"Ohtani T","year":"2000","journal-title":"Anticancer Res."},{"key":"e_1_2_5_15_2","first-page":"243","article-title":"The chemotherapeutic drug 5\u2010fluorouracil induces apoptosis in mouse thymocytes in vivo via activation of CD95(APO\u20101\/Fas) system","volume":"61","author":"Eichhorst ST","year":"2001","journal-title":"Cancer Res."},{"key":"e_1_2_5_16_2","doi-asserted-by":"publisher","DOI":"10.1054\/bjoc.2000.1455"},{"key":"e_1_2_5_17_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.3072"},{"key":"e_1_2_5_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19900815)66:4<684::AID-CNCR2820660416>3.0.CO;2-X"},{"key":"e_1_2_5_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0609.1988.tb00799.x"},{"key":"e_1_2_5_20_2","first-page":"46","volume-title":"In vitro biological methods, methods in toxicology","author":"Rose K","year":"1992"},{"key":"e_1_2_5_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/0962-8924(93)90213-K"},{"key":"e_1_2_5_22_2","doi-asserted-by":"publisher","DOI":"10.1097\/00019052-200106000-00001"},{"key":"e_1_2_5_23_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5381.1302"},{"key":"e_1_2_5_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.1126"},{"key":"e_1_2_5_25_2","doi-asserted-by":"publisher","DOI":"10.1080\/009841000156709"},{"key":"e_1_2_5_26_2","first-page":"163","article-title":"5\u2010Fluorouracil cytotoxicity in human colon HT\u201029 cells with moderately increased or decreased cellular glutathione level","volume":"15","author":"Chen MF","year":"1995","journal-title":"Anticancer Res."},{"key":"e_1_2_5_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1197-1233"},{"key":"e_1_2_5_28_2","doi-asserted-by":"publisher","DOI":"10.1159\/000188853"},{"key":"e_1_2_5_29_2","first-page":"4387","article-title":"Inhibition of Adriamycin cardiotoxicity by 5\u2010fluorouracil: a potential free oxygen radical scavenger","volume":"18","author":"Stathopoulos GP","year":"1998","journal-title":"Anticancer Res."},{"key":"e_1_2_5_30_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.27.9.1641"},{"key":"e_1_2_5_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0398-291"}],"container-title":["Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcncr.20114","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.20114","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T08:43:04Z","timestamp":1760258584000},"score":1,"resource":{"primary":{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/10.1002\/cncr.20114"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,2,26]]},"references-count":30,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2004,4]]}},"alternative-id":["10.1002\/cncr.20114"],"URL":"https:\/\/doi.org\/10.1002\/cncr.20114","archive":["Portico"],"relation":{},"ISSN":["0008-543X","1097-0142"],"issn-type":[{"value":"0008-543X","type":"print"},{"value":"1097-0142","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,2,26]]}}}