{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T03:01:11Z","timestamp":1780628471661,"version":"3.54.1"},"reference-count":59,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,10,28]],"date-time":"2015-10-28T00:00:00Z","timestamp":1445990400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001513","name":"Cancer Society of New Zealand","doi-asserted-by":"publisher","award":["10\/23"],"award-info":[{"award-number":["10\/23"]}],"id":[{"id":"10.13039\/501100001513","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001505","name":"Health Research Council of New Zealand","doi-asserted-by":"publisher","award":["12\/254"],"award-info":[{"award-number":["12\/254"]}],"id":[{"id":"10.13039\/501100001505","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Platinum\u2010based anticancer drugs cause peripheral neurotoxicity by damaging sensory neurons within the dorsal root ganglia (DRG), but the mechanisms are incompletely understood. The roles of platinum DNA binding, transcription inhibition and altered cell size were investigated in primary cultures of rat DRG cells. Click chemistry quantitative fluorescence imaging of RNA\u2010incorporated 5\u2010ethynyluridine showed high, but wide ranging, global levels of transcription in individual neurons that correlated with their cell body size. Treatment with platinum drugs reduced neuronal transcription and cell body size to an extent that corresponded to the amount of preceding platinum DNA binding, but without any loss of neuronal cells. The effects of platinum drugs on neuronal transcription and cell body size were inhibited by blocking platinum DNA binding with sodium thiosulfate, and mimicked by treatment with a model transcriptional inhibitor, actinomycin D. <jats:italic>In vivo<\/jats:italic> oxaliplatin treatment depleted the total RNA content of DRG tissue concurrently with altering DRG neuronal size. These findings point to a mechanism of chemotherapy\u2010induced peripheral neurotoxicity, whereby platinum DNA damage induces global transcriptional arrest leading in turn to neuronal atrophy. DRG neurons may be particularly vulnerable to this mechanism of toxicity because of their requirements for high basal levels of global transcriptional activity.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc13355-fig-0009-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>Findings point to a new stepwise mechanism of chemotherapy\u2010induced peripheral neurotoxicity, whereby platinum DNA damage induces global transcriptional arrest leading in turn to neuronal atrophy. Dorsal root ganglion neurons may be particularly vulnerable to this neurotoxicity because of their high global transcriptional outputs, demonstrated in this study by click chemistry quantitative fluorescence imaging.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.13355","type":"journal-article","created":{"date-parts":[[2015,9,14]],"date-time":"2015-09-14T08:43:01Z","timestamp":1442220181000},"page":"1099-1112","source":"Crossref","is-referenced-by-count":34,"title":["Role of platinum DNA damage\u2010induced transcriptional inhibition in chemotherapy\u2010induced neuronal atrophy and peripheral neurotoxicity"],"prefix":"10.1111","volume":"135","author":[{"given":"Fang","family":"Yan","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Clinical Pharmacology School of Medical Sciences Faculty of Medical and Health Sciences University of Auckland Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johnson J","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Clinical Pharmacology School of Medical Sciences Faculty of Medical and Health Sciences University of Auckland Auckland New Zealand"},{"name":"School of Medicine Faculty of Health University of Tasmania Hobart Tasmania Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia","family":"Ip","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Clinical Pharmacology School of Medical Sciences Faculty of Medical and Health Sciences University of Auckland Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen M F","family":"Jamieson","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Clinical Pharmacology School of Medical Sciences Faculty of Medical and Health Sciences University of Auckland Auckland New Zealand"},{"name":"Auckland Cancer Society Research Centre School of Medical Sciences Faculty of Medical and Health Sciences University of Auckland Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J","family":"McKeage","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Clinical Pharmacology School of Medical Sciences Faculty of Medical and Health Sciences University of Auckland Auckland New Zealand"},{"name":"Auckland Cancer Society Research Centre School of Medical Sciences Faculty of Medical and Health Sciences University of Auckland Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,10,28]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja101495v"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2014-0044"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.4161\/trns.2.3.16172"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsb.2006.12.008"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00216-008-2034-8"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt502"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00684664"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00227662"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-8049(01)00300-8"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4886(72)90226-9"},{"key":"e_1_2_7_12_1","first-page":"253","article-title":"An overview of ABC and SLC drug transporter gene regulation","volume":"14","author":"Chen Q. X.","year":"2013","journal-title":"Curr. Drug Metab."},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/269527a0"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0523-07.2007"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1006\/nbdi.2001.0426"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.142.5.1313"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E10-08-0731"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI1130"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M301554200"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2008.05550.x"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-13-495"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2010.01.046"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2011.07231.x"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2010.06859.x"},{"key":"e_1_2_7_25_1","first-page":"342","article-title":"Comparative neurotoxicity of oxaliplatin, cisplatin, and ormaplatin in a Wistar rat model","volume":"46","author":"Holmes J.","year":"1998","journal-title":"Toxicol. Sci."},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1039\/b716925f"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/1440-1681.12088"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-004-0953-4"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0808480105"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.111.181297"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/26.12.2831"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr068207j"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0106485"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2990.1999.00160.x"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2012.10.023"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2012.07.003"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0081162"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1006\/nbdi.2001.0468"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2004.09.013"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1054\/bjoc.2001.2024"},{"key":"e_1_2_7_41_1","first-page":"883","article-title":"Cisplatin\u2010induced DNA\u2010platination in experimental dorsal root ganglia neuronopathy","volume":"20","author":"Meijer C.","year":"1999","journal-title":"Neurotoxicology"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/0009-2797(81)90181-2"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2010.11.017"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-7-29"},{"key":"e_1_2_7_45_1","volume-title":"Sensory Neurons: Diversity, Development and Plasticity","author":"Scott S. A.","year":"1992"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0162-0134(99)00135-X"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1997.416"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1054\/bjoc.1999.1026"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00340295"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(05)70096-X"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2006.04.010"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1039\/b907567d"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00688308"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.12.5672"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001813-199904000-00011"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/16.24.7444"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1691"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-004-1277-2"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/0169-328X(94)90198-8"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-13-0198"}],"container-title":["Journal of Neurochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjnc.13355","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjnc.13355","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jnc.13355","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T19:45:49Z","timestamp":1696275949000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jnc.13355"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,10,28]]},"references-count":59,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2015,12]]}},"alternative-id":["10.1111\/jnc.13355"],"URL":"https:\/\/doi.org\/10.1111\/jnc.13355","archive":["Portico"],"relation":{},"ISSN":["0022-3042","1471-4159"],"issn-type":[{"value":"0022-3042","type":"print"},{"value":"1471-4159","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,10,28]]}}}