{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T11:36:27Z","timestamp":1777894587413,"version":"3.51.4"},"reference-count":37,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2001,4,1]],"date-time":"2001-04-01T00:00:00Z","timestamp":986083200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxicol Pathol"],"published-print":{"date-parts":[[2001,4]]},"abstract":"<jats:p>\n                    Japanese medaka fish ( Oryzias latipes) were used to develop an in vivo method to assess hepatocellular proliferation in a nonmammalian model. Proliferative responses were assessed in medaka at 7, 17, 24, and 94 days after a 48-hour exposure to 10 or 100 mg\/L diethylnitrosamine (DEN). Subgroups of medaka were exposed to 50 or 75 mg\/L of 5-bromo-2'-deoxyuridine (BrdU) in water for 72 hours, sacrificed, and then processed for immunohistochemical staining. Proliferative indices of BrdU-labeled hepatocytes were quantified and compared using both count and area measurements. There was a significant increase ( p &lt; 0.05) in hepatocellular proliferation in the 100 mg\/L DEN-treated fish as compared to controls and 10 mg\/L DEN-treated fish for the first 3 time points. Hepatocarcinogenicit y was evaluated 26 weeks post-DEN exposure. There was a significant increase ( p &lt; 0.0001) in hepatocellular neoplasms in 100 mg\/L DEN-treated fish compared to other fish. Effective BrdU-labeling of S-phase hepatocytes in medaka was achieved by adding BrdU to the aquarium water, and an increase in hepatocellular proliferation using this method was detected 7 days after exposure to a carcinogenic concentration of DEN. Additionally, the new method of area measurement indices of proliferation were as precise as count indices (R\n                    <jats:sup>2<\/jats:sup>\n                    \u22650.92).\n                  <\/jats:p>","DOI":"10.1080\/019262301316905354","type":"journal-article","created":{"date-parts":[[2003,1,29]],"date-time":"2003-01-29T23:23:13Z","timestamp":1043882593000},"page":"387-397","source":"Crossref","is-referenced-by-count":4,"title":["An In Vivo Method for Using 5-Bromo-2'-deoxyuridine (BrdU) as a Marker of Chemically-Induced Hepatocellular Proliferation in the Japanese Medaka (Oryzias latipes)"],"prefix":"10.1177","volume":"29","author":[{"given":"Linda M.","family":"Brennan","sequence":"first","affiliation":[{"name":"GEO-CENTERS, INC, Fort Detrick, Maryland 21702-5010"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E. Maxine","family":"Boncavage-Hennessey","sequence":"additional","affiliation":[{"name":"GEO-CENTERS, INC, Fort Collins, Colorado 80523"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marilyn J.","family":"Wolfe","sequence":"additional","affiliation":[{"name":"Experimental Pathology Laboratories, Herndon, Virginia 20172"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margaret W.","family":"Toussaint","sequence":"additional","affiliation":[{"name":"GEO-CENTERS, INC, Fort Detrick, Maryland 21702-5010"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William E.","family":"Dennis","sequence":"additional","affiliation":[{"name":"GEO-CENTERS, INC, Fort Detrick, Maryland 21702-5010"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan B.","family":"Rosencrance","sequence":"additional","affiliation":[{"name":"US Army Center for Environmental Health Research, Fort Detrick, Maryland 21702-5010"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"JR","given":"Henry S.","family":"Gardner","sequence":"additional","affiliation":[{"name":"US Army Center for Environmental Health Research, Fort Detrick, Maryland 21702-5010,"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2001,4,1]]},"reference":[{"key":"atypb1","first-page":"369","volume":"28","author":"Bunton TE","year":"1989","journal-title":"Environ Res"},{"key":"atypb2","doi-asserted-by":"publisher","DOI":"10.1177\/019262339001800210"},{"key":"atypb3","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4800(91)90022-P"},{"key":"atypb4","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3835(89)90086-4"},{"key":"atypb5","doi-asserted-by":"publisher","DOI":"10.1177\/41.1.7678022"},{"key":"atypb6","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/16.2.303"},{"key":"atypb7","doi-asserted-by":"publisher","DOI":"10.1016\/0041-008X(91)90050-O"},{"key":"atypb8","doi-asserted-by":"publisher","DOI":"10.1016\/0166-445X(88)90040-9"},{"key":"atypb9","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/12.9.1557"},{"key":"atypb10","doi-asserted-by":"publisher","DOI":"10.1016\/0041-008X(85)90135-8"},{"key":"atypb11","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/11.12.2245"},{"key":"atypb12","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/14.7.1285"},{"key":"atypb13","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.98106s61299"},{"key":"atypb14","unstructured":"Goldsworthy TL , Morgan KT, Popp JA, Butterworth BE (1991). Guidelines for measuring chemically induced cell proliferation in specific rodent target organs. In: Chemically Induced Cell Proliferation: Implications for Risk Assessment , Butterworth BE, Slaga TJ, Farland W, McClain M (eds). Wiley-Liss, Inc, New York, pp 253\u2014284."},{"key":"atypb15","doi-asserted-by":"publisher","DOI":"10.1016\/0166-445X(88)90009-4"},{"key":"atypb16","doi-asserted-by":"publisher","DOI":"10.3109\/15376519509084029"},{"key":"atypb17","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.15.5955"},{"key":"atypb18","doi-asserted-by":"publisher","DOI":"10.1177\/40.5.1573246"},{"key":"atypb19","doi-asserted-by":"publisher","DOI":"10.1006\/faat.1993.1021"},{"key":"atypb20","doi-asserted-by":"publisher","DOI":"10.1007\/BF02890404"},{"key":"atypb21","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/17.8.1657"},{"key":"atypb22","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/14.3.399"},{"key":"atypb23","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/10.7.1341"},{"key":"atypb24","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/19.3.515"},{"key":"atypb25","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/16.4.841"},{"key":"atypb26","first-page":"13","volume":"34","author":"Moore MJ","year":"1992","journal-title":"Environ Res"},{"key":"atypb27","doi-asserted-by":"publisher","DOI":"10.1016\/0166-445X(94)90013-2"},{"key":"atypb28","volume-title":"Guide for the Care and Use of Laboratory Animals","author":"National Research Council","year":"1996"},{"key":"atypb29","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3835(89)90018-9"},{"key":"atypb30","doi-asserted-by":"publisher","DOI":"10.3354\/dao008211"},{"key":"atypb31","first-page":"561","volume":"1","author":"Richter F.","year":"1992","journal-title":"Cancer Epidemiol Biomark Prevent"},{"key":"atypb32","doi-asserted-by":"publisher","DOI":"10.1007\/BF00494803"},{"key":"atypb33","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.1989.tb02257.x"},{"key":"atypb34","doi-asserted-by":"publisher","DOI":"10.1177\/019262339902700607"},{"key":"atypb35","unstructured":"Ward JM, Weghorst CM, Diwan BA, Konishi N., Lubet RA, Henneman JR, Devor DE (1991). Evaluation of cell proliferation in the kidneys of rodents with bromodeoxyuridine immunohistochemistry or tritiated thymidine autoradiography after exposure to renal toxins, tumor promoters, and carcinogens . In: Chemically Induced Cell Proliferation: Implications for Risk Assessment. Butterworth BE, Slaga TJ, Farland W, McClain M (eds). Wiley-Liss, Inc, New York, pp 369\u2014388."},{"key":"atypb36","doi-asserted-by":"publisher","DOI":"10.1177\/39.2.1987261"},{"key":"atypb37","first-page":"555","volume":"115","author":"Woosley JT","year":"1991","journal-title":"Arch Pathol Lab Med"}],"container-title":["Toxicologic Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1080\/019262301316905354","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1080\/019262301316905354","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T07:25:55Z","timestamp":1777620355000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1080\/019262301316905354"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,4]]},"references-count":37,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2001,4]]}},"alternative-id":["10.1080\/019262301316905354"],"URL":"https:\/\/doi.org\/10.1080\/019262301316905354","relation":{},"ISSN":["0192-6233","1533-1601"],"issn-type":[{"value":"0192-6233","type":"print"},{"value":"1533-1601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,4]]}}}