{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,8]],"date-time":"2026-11-08T04:02:32Z","timestamp":1794110552659,"version":"4.8.0"},"reference-count":32,"publisher":"Society for Neuroscience","issue":"35","license":[{"start":{"date-parts":[[2008,2,29]],"date-time":"2008-02-29T00:00:00Z","timestamp":1204243200000},"content-version":"vor","delay-in-days":184,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2007,8,29]]},"abstract":"<jats:p>The pronounced neurotoxicity of the potent antitumor drug cisplatin frequently results in the onset of peripheral polyneuropathy (PNP), which is assumed to be initially triggered by platination products in the nuclear DNA of affected tissues. To further elucidate the molecular mechanisms, we analyzed in a mouse model the formation and processing of the main cisplatin-induced DNA adduct (guanine\u2013guanine intrastrand cross-link) in distinct neuronal cell types by adduct-specific monoclonal antibodies. Comparison of the adduct kinetics in cisplatin-injected mice either proficient or deficient for nucleotide excision repair (NER) functions revealed the essential role of this DNA repair pathway in protecting differentiated cells of the nervous system from excessive formation of such lesions. Hence, chronic exposure to cisplatin resulted in an accelerated accumulation of unrepaired intrastrand cross-links in neuronal cells of mice with dysfunctional NER. The augmented adduct levels in dorsal root ganglion (DRG) cells of those animals coincided with an earlier onset of PNP-like functional disturbance of their sensory nervous system. Independently from the respective repair phenotype, the amount of persisting DNA cross-links in DRG neurons at a given cumulative dose was significantly correlated to the degree of sensory impairment as measured by electroneurography. Collectively, these findings suggest a new model for the processing of cisplatin adducts in primary neuronal cells and accentuate the crucial role of effectual DNA repair capacity in the target cells for the individual risk of therapy-induced PNP.<\/jats:p>","DOI":"10.1523\/jneurosci.0523-07.2007","type":"journal-article","created":{"date-parts":[[2007,8,29]],"date-time":"2007-08-29T16:24:00Z","timestamp":1188404640000},"page":"9451-9457","source":"Crossref","is-referenced-by-count":133,"title":["Repair Capacity for Platinum-DNA Adducts Determines the Severity of Cisplatin-Induced Peripheral Neuropathy"],"prefix":"10.1523","volume":"27","author":[{"given":"Anna","family":"Dzagnidze","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaza","family":"Katsarava","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Makhalova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Liedert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Suk","family":"Yoon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Kaube","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volker","family":"Limmroth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juergen","family":"Thomale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2007,8,29]]},"reference":[{"key":"2023041303270998000_27.35.9451.1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.1998.00173.x"},{"key":"2023041303270998000_27.35.9451.2","first-page":"1663","article-title":"Cisplatin and platinum drugs at the molecular level. Review","volume":"10","author":"Boulikas","year":"2003","journal-title":"Oncol Rep"},{"key":"2023041303270998000_27.35.9451.3","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-01-0022"},{"key":"2023041303270998000_27.35.9451.4","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.1999.00523.x"},{"key":"2023041303270998000_27.35.9451.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2006.04.025"},{"key":"2023041303270998000_27.35.9451.6","doi-asserted-by":"publisher","DOI":"10.1016\/0041-008X(87)90178-5"},{"key":"2023041303270998000_27.35.9451.7","first-page":"4899","article-title":"Transcription-coupled nucleotide excision repair as a determinant of cisplatin sensitivity of human cells","volume":"62","author":"Furuta","year":"2002","journal-title":"Cancer Res"},{"key":"2023041303270998000_27.35.9451.8","doi-asserted-by":"crossref","first-page":"2842","DOI":"10.1172\/JCI1130","article-title":"Cisplatin-induced apoptosis in rat dorsal root ganglion neurons is associated with attempted entry into the cell cycle","volume":"101","author":"Gill","year":"1998","journal-title":"J Clin Invest"},{"key":"2023041303270998000_27.35.9451.9","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1200\/JCO.1992.10.5.795","article-title":"Cisplatin neurotoxicity: the relationship between dosage, time, and platinum concentration in neurologic tissues, and morphologic evidence of toxicity","volume":"10","author":"Gregg","year":"1992","journal-title":"J Clin Oncol"},{"key":"2023041303270998000_27.35.9451.10","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1200\/JCO.1989.7.10.1457","article-title":"Long-term neurotoxicity in patients treated with cisplatin, vinblastine, and bleomycin for metastatic germ cell cancer","volume":"7","author":"Hansen","year":"1989","journal-title":"J Clin Oncol"},{"key":"2023041303270998000_27.35.9451.11","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/116.5.1017"},{"key":"2023041303270998000_27.35.9451.12","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2006.097899"},{"key":"2023041303270998000_27.35.9451.13","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkl051"},{"key":"2023041303270998000_27.35.9451.14","doi-asserted-by":"publisher","DOI":"10.1007\/BF00839140"},{"key":"2023041303270998000_27.35.9451.15","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.20899"},{"key":"2023041303270998000_27.35.9451.16","doi-asserted-by":"publisher","DOI":"10.1006\/nbdi.2001.0468"},{"key":"2023041303270998000_27.35.9451.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2004.09.013"},{"key":"2023041303270998000_27.35.9451.18","first-page":"883","article-title":"Cisplatin-induced DNA-platination in experimental dorsal root ganglia neuronopathy","volume":"20","author":"Meijer","year":"1999","journal-title":"Neurotoxicology"},{"key":"2023041303270998000_27.35.9451.19","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1056\/NEJM199001113220210","article-title":"Cisplatin neurotoxicity","volume":"322","author":"Mollman","year":"1990","journal-title":"N Engl J Med"},{"key":"2023041303270998000_27.35.9451.20","doi-asserted-by":"publisher","DOI":"10.1038\/377165a0"},{"key":"2023041303270998000_27.35.9451.21","doi-asserted-by":"publisher","DOI":"10.1016\/S1568-7864(01)00005-2"},{"key":"2023041303270998000_27.35.9451.22","first-page":"718","article-title":"cis-Diamminedichloroplatinum (II)-DNA adduct formation in renal, gonadal, and tumor tissues of male and female rats","volume":"47","author":"Reed","year":"1987","journal-title":"Cancer Res"},{"key":"2023041303270998000_27.35.9451.23","first-page":"18","article-title":"Adult-onset xeroderma pigmentosum neurological disease\u2014observations in an autopsy case","volume":"21","author":"Robbins","year":"2002","journal-title":"Clin Neuropathol"},{"key":"2023041303270998000_27.35.9451.24","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.critrevonc.2004.09.007","article-title":"Copper transporters regulate the cellular pharmacology and sensitivity to Pt drugs","volume":"53","author":"Safaei","year":"2005","journal-title":"Crit Rev Oncol Hematol"},{"key":"2023041303270998000_27.35.9451.25","doi-asserted-by":"publisher","DOI":"10.1016\/S0162-0134(99)00135-X"},{"key":"2023041303270998000_27.35.9451.26","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1206933"},{"key":"2023041303270998000_27.35.9451.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2006.04.010"},{"key":"2023041303270998000_27.35.9451.28","doi-asserted-by":"publisher","DOI":"10.1124\/mol.106.022244"},{"key":"2023041303270998000_27.35.9451.29","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19841001)54:7<1269::AID-CNCR2820540707>3.0.CO;2-9"},{"key":"2023041303270998000_27.35.9451.30","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4598(199903)22:3<329::AID-MUS5>3.0.CO;2-8"},{"key":"2023041303270998000_27.35.9451.31","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.20134"},{"key":"2023041303270998000_27.35.9451.32","doi-asserted-by":"publisher","DOI":"10.1101\/sqb.2000.65.173"}],"container-title":["The Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.0523-07.2007","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T18:14:21Z","timestamp":1681409661000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jneurosci.org\/lookup\/doi\/10.1523\/JNEUROSCI.0523-07.2007"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,8,29]]},"references-count":32,"journal-issue":{"issue":"35","published-online":{"date-parts":[[2007,8,29]]},"published-print":{"date-parts":[[2007,8,29]]}},"alternative-id":["10.1523\/JNEUROSCI.0523-07.2007"],"URL":"https:\/\/doi.org\/10.1523\/jneurosci.0523-07.2007","relation":{},"ISSN":["0270-6474","1529-2401"],"issn-type":[{"value":"0270-6474","type":"print"},{"value":"1529-2401","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,8,29]]}}}