{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T14:58:26Z","timestamp":1773759506693,"version":"3.50.1"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":7428,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1995,5]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>Detection of DNA fragments <jats:italic toggle=\"yes\">in situ<\/jats:italic> using the terminal deoxyribonucleotidyl transferase (TDT)-mediated dUTP-digoxigenin nick end labeling (TUNEL) assay is increasingly applied to investigate active cell death (apoptosis). We studied the specificity of the assay in well-defined models of apoptosis and necrosis as well as in postmortem autolysis in rat liver. During involution of liver hyperplasia, which follows stopping treatment with the hepatomitogens cyproterone acetate (CPA) or nafenopin (NAF), numerous apoptotic hepatocytes could be observed with TUNEL-positive chromatin residues. A similar TUNEL-positive reaction appeared in necrotic hepatocytes after a cytotoxic dose of carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>) or <jats:italic toggle=\"yes\">N<\/jats:italic>-nitrosomorpholine (NNM). Also, in insufficiently fixed, autolytic livers TUNEL-positive nuclei were observed. Thus, DNA fragmentation is common to different kinds of cell death; its detection <jats:italic toggle=\"yes\">in situ<\/jats:italic> should not be considered a specific marker of apoptosis.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.1840210534","type":"journal-article","created":{"date-parts":[[2007,3,4]],"date-time":"2007-03-04T04:09:40Z","timestamp":1172981380000},"page":"1465-1468","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":110,"title":["In situ detection of fragmented dna (tunel assay) fails to discriminate among apoptosis, necrosis, and autolytic cell death: A cautionary note"],"prefix":"10.1097","volume":"21","author":[{"given":"Bettina Grasl","family":"Kraupp","sequence":"first","affiliation":[]},{"given":"Branislav","family":"Ruttkay-Nedecky","sequence":"additional","affiliation":[]},{"given":"Helga","family":"Koudelka","sequence":"additional","affiliation":[]},{"given":"Krystyna","family":"Bukowska","sequence":"additional","affiliation":[]},{"given":"Wilfried","family":"Bursch","sequence":"additional","affiliation":[]},{"given":"Rolf","family":"Schulte-Hermann","sequence":"additional","affiliation":[]}],"member":"276","reference":[{"key":"10.1002\/hep.1840210534-BIB1","first-page":"115","volume-title":"Progress in liver disease","author":"Fausto","year":"1993","unstructured":". Mechanisms of growth regulation in liver regeneration and hepatic carcinogenesis. In: , eds. Progress in liver disease. Vol XI. Philadelphia: Grune & Stratton, 1993: 115\u2013137."},{"key":"10.1002\/hep.1840210534-BIB2","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1096\/fasebj.4.2.2404819","volume":"4","author":"Michalopoulos","year":"1990","journal-title":"FASEB J"},{"key":"10.1002\/hep.1840210534-BIB3","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1083\/jcb.126.1.223","volume":"126","author":"Nagy","year":"1994","journal-title":"J Cell Biol"},{"key":"10.1002\/hep.1840210534-BIB4","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1002\/hep.1840170626","volume":"17","author":"Conti","year":"1993","journal-title":"Hepatology"},{"key":"10.1002\/hep.1840210534-BIB5","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1006\/bbrc.1993.1772","volume":"193","author":"Li","year":"1993","journal-title":"Biochem Biophys Res Comm"},{"key":"10.1002\/hep.1840210534-BIB6","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/bjc.1972.33","volume":"26","author":"Kerr","year":"1972","journal-title":"Br J Cancer"},{"key":"10.1002\/hep.1840210534-BIB7","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/0165-6147(92)90077-J","volume":"13","author":"Bursch","year":"1992","journal-title":"Trends Pharmacol Sci"},{"key":"10.1002\/hep.1840210534-BIB8","doi-asserted-by":"crossref","first-page":"9995","DOI":"10.1073\/pnas.91.21.9995","volume":"91","author":"Grasl-Kraupp","year":"1994","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1002\/hep.1840210534-BIB9","doi-asserted-by":"crossref","first-page":"5408","DOI":"10.1073\/pnas.89.12.5408","volume":"89","author":"Oberhammer","year":"1992","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1002\/hep.1840210534-BIB10","first-page":"347","volume":"18","author":"Schwall","year":"1993","journal-title":"Hepatology"},{"key":"10.1002\/hep.1840210534-BIB11","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1136\/gut.35.5.577","volume":"35","author":"Alison","year":"1994","journal-title":"Gut"},{"key":"10.1002\/hep.1840210534-BIB12","first-page":"67","volume":"32","author":"Schaff","year":"1984","journal-title":"Acta Morphol Hung"},{"key":"10.1002\/hep.1840210534-BIB13","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.4049\/jimmunol.153.4.1778","volume":"153","author":"Leist","year":"1994","journal-title":"J Immunol"},{"key":"10.1002\/hep.1840210534-BIB14","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1038\/364806a0","volume":"364","author":"Ogasawara","year":"1993","journal-title":"Nature"},{"key":"10.1002\/hep.1840210534-BIB15","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1038\/284555a0","volume":"284","author":"Wyllie","year":"1980","journal-title":"Nature"},{"key":"10.1002\/hep.1840210534-BIB16","doi-asserted-by":"crossref","first-page":"3679","DOI":"10.1002\/j.1460-2075.1993.tb06042.x","volume":"12","author":"Oberhammer","year":"1993","journal-title":"EMBO J"},{"key":"10.1002\/hep.1840210534-BIB17","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1006\/excr.1994.1178","volume":"213","author":"Walker","year":"1994","journal-title":"Exp Cell Res"},{"key":"10.1002\/hep.1840210534-BIB18","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/0014-5793(94)80001-4","volume":"349","author":"Cain","year":"1994","journal-title":"FEBS Lett"},{"key":"10.1002\/hep.1840210534-BIB19","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1242\/jcs.104.2.317","volume":"104","author":"Oberhammer","year":"1993","journal-title":"J Cell Sci"},{"key":"10.1002\/hep.1840210534-BIB20","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1083\/jcb.119.3.493","volume":"119","author":"Gavrieli","year":"1992","journal-title":"J Cell Biol"},{"key":"10.1002\/hep.1840210534-BIB21","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1177\/41.7.8515045","volume":"41","author":"Gold","year":"1993","journal-title":"J Histochem Cytochem"},{"key":"10.1002\/hep.1840210534-BIB22","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1177\/41.1.7678025","volume":"41","author":"Wijsman","year":"1993","journal-title":"J Histochem Cytochem"},{"key":"10.1002\/hep.1840210534-BIB23","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1002\/hep.1840180533","volume":"18","author":"Oberhammer","year":"1993","journal-title":"Hepatology"},{"key":"10.1002\/hep.1840210534-BIB24","first-page":"1945","volume":"53","author":"Gorczyca","year":"1993","journal-title":"Cancer Res"},{"key":"10.1002\/hep.1840210534-BIB25","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/BF02889898","volume":"50","author":"Bursch","year":"1985","journal-title":"Virch Arch Cell Pathol"},{"key":"10.1002\/hep.1840210534-BIB26","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/0041-008X(91)90028-D","volume":"111","author":"Shen","year":"1991","journal-title":"Toxicol Appl Pharmacol"},{"key":"10.1002\/hep.1840210534-BIB27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/path.1711700102","volume":"170","author":"Ansari","year":"1993","journal-title":"J Pathol"},{"key":"10.1002\/hep.1840210534-BIB28","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1080\/09553009214551201","volume":"61","author":"Collins","year":"1992","journal-title":"Int J Radiat Biol"},{"key":"10.1002\/hep.1840210534-BIB29","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1084\/jem.179.2.559","volume":"179","author":"Sun","year":"1994","journal-title":"J Exp Med"},{"key":"10.1002\/hep.1840210534-BIB30","first-page":"918","volume":"143","author":"Tsukidate","year":"1993","journal-title":"Am J Pathol"},{"key":"10.1002\/hep.1840210534-BIB31","first-page":"219","volume":"71","author":"Gold","year":"1994","journal-title":"Lab Invest"},{"key":"10.1002\/hep.1840210534-BIB32","first-page":"281","volume":"10","author":"Orrenius","year":"1989","journal-title":"TIPS"},{"key":"10.1002\/hep.1840210534-BIB33","first-page":"209","volume-title":"Progress in liver disease","author":"Popper","year":"1986","unstructured":". Networks of interacting mechanisms of hepatocellular degeneration and death. In: . eds. Progress in liver disease. Vol VIII. Philadelphia: Grune & Stratton, 1986: 209\u2013235."},{"key":"10.1002\/hep.1840210534-BIB34","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1093\/carcin\/11.5.847","volume":"11","author":"Bursch","year":"1990","journal-title":"Carcinogenesis"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.1840210534","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-199505000-00033","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T11:19:16Z","timestamp":1733051956000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-199505000-00033"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,5]]},"references-count":34,"journal-issue":{"issue":"5","published-print":{"date-parts":[[1995]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.1840210534","relation":{},"ISSN":["0270-9139"],"issn-type":[{"value":"0270-9139","type":"print"}],"subject":[],"published":{"date-parts":[[1995,5]]}}}