{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T16:58:42Z","timestamp":1777913922358,"version":"3.51.4"},"reference-count":21,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2014,10,1]],"date-time":"2014-10-01T00:00:00Z","timestamp":1412121600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Toxicol Pathol"],"published-print":{"date-parts":[[2015,6]]},"abstract":"<jats:p>Batracylin (NSC-320846) is a dual inhibitor of DNA topoisomerases I and II. Batracylin advanced as an anticancer agent to Phase I clinical trials where dose limiting hemorrhagic cystitis (bladder inflammation and bleeding) was observed. To further investigate batracylin\u2019s mechanism of toxicity, studies were conducted in Fischer 344 rats. Once daily oral administration of 16 or 32 mg\/kg batracylin to rats for 4 days caused overt toxicity. Abnormal clinical observations and adverse effects on clinical pathology, urinalysis, and histology indicated acute renal damage and urothelial damage and bone marrow dysfunction. Scanning electron microscopy revealed sloughing of the superficial and intermediate urothelial layers. DNA damage was evident in kidney and bone marrow as indicated by histone \u03b3-H2AX immunofluorescence. After a single oral administration of 16 or 32 mg\/kg, the majority of batracylin was converted to N-acetylbatracylin (NAB) with a half-life of 4 hr to 11 hr. Mesna (Mesnex\u2122), a drug known to reduce the incidence of hemorrhagic cystitis induced by ifosfamide or cyclophosphamide, was administered to rats prior to batracylin, but did not alleviate batracylin-induced bladder and renal toxicity. These findings suggest that batracylin results in DNA damage-based mechanisms of toxicity and not an acrolein-based mechanism of toxicity as occurs after ifosfamide or cyclophosphamide administration.<\/jats:p>","DOI":"10.1177\/0192623314548766","type":"journal-article","created":{"date-parts":[[2014,10,2]],"date-time":"2014-10-02T02:48:30Z","timestamp":1412218110000},"page":"519-529","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["Characterization of Batracylin-induced Renal and Bladder Toxicity in Rats"],"prefix":"10.1177","volume":"43","author":[{"given":"Myrtle","family":"Davis","sequence":"first","affiliation":[{"name":"Toxicology and Pharmacology Branch, Division of Cancer Treatment and Diagnosis, The National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah I.","family":"Bunin","sequence":"additional","affiliation":[{"name":"SRI International, Menlo Park, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven J.","family":"Samuelsson","sequence":"additional","affiliation":[{"name":"SRI International, Menlo Park, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth P.","family":"Altera","sequence":"additional","affiliation":[{"name":"SRI International, Menlo Park, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert J.","family":"Kinders","sequence":"additional","affiliation":[{"name":"Pharmacodynamics Assay Development and Implementation Section, Laboratory of Human Toxicology and Pharmacology, Applied\/Developmental Research Directorate, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott M.","family":"Lawrence","sequence":"additional","affiliation":[{"name":"Pharmacodynamics Assay Development and Implementation Section, Laboratory of Human Toxicology and Pharmacology, Applied\/Developmental Research Directorate, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiuping","family":"Ji","sequence":"additional","affiliation":[{"name":"Pharmacodynamics Assay Development and Implementation Section, Laboratory of Human Toxicology and Pharmacology, Applied\/Developmental Research Directorate, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew M.","family":"Ames","sequence":"additional","affiliation":[{"name":"Department of Oncology, Division of Oncology Research, Mayo Clinic, Rochester, Minnesota"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah A.","family":"Buhrow","sequence":"additional","affiliation":[{"name":"Department of Oncology, Division of Oncology Research, Mayo Clinic, Rochester, Minnesota"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chad","family":"Walden","sequence":"additional","affiliation":[{"name":"Department of Oncology, Division of Oncology Research, Mayo Clinic, Rochester, Minnesota"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joel M.","family":"Reid","sequence":"additional","affiliation":[{"name":"Department of Oncology, Division of Oncology Research, Mayo Clinic, Rochester, Minnesota"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda L.","family":"Rausch","sequence":"additional","affiliation":[{"name":"SRI International, Menlo Park, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toufan","family":"Parman","sequence":"additional","affiliation":[{"name":"SRI International, Menlo Park, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2014,10,1]]},"reference":[{"key":"bibr1-0192623314548766","doi-asserted-by":"publisher","DOI":"10.1007\/BF00176974"},{"key":"bibr2-0192623314548766","doi-asserted-by":"publisher","DOI":"10.1007\/BF00410691"},{"key":"bibr3-0192623314548766","doi-asserted-by":"publisher","DOI":"10.1080\/01926230701197115"},{"key":"bibr4-0192623314548766","doi-asserted-by":"publisher","DOI":"10.1038\/nature07849"},{"key":"bibr40-0192623314548766","unstructured":"Dixit R., Stedham M., Maldinger B., Lopez R., El-hawari M. (1989). Nine daily dose study of Batracylin (NSC-320846) in beagle dogs. Retrieved from National Technical Information Service website: http:\/\/www.ntis.gov."},{"key":"bibr5-0192623314548766","doi-asserted-by":"publisher","DOI":"10.2174\/092986712803251502"},{"key":"bibr6-0192623314548766","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1990.8.1.170"},{"key":"bibr7-0192623314548766","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-11-1227"},{"key":"bibr8-0192623314548766","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-013-2244-4"},{"key":"bibr9-0192623314548766","doi-asserted-by":"publisher","DOI":"10.1023\/A:1018929815422"},{"key":"bibr10-0192623314548766","doi-asserted-by":"publisher","DOI":"10.1021\/jm00046a028"},{"key":"bibr11-0192623314548766","doi-asserted-by":"publisher","DOI":"10.1007\/BF00173759"},{"key":"bibr12-0192623314548766","unstructured":"National Cancer Institute. Accessed September 13, 20121. http:\/\/dctd.cancer.gov\/FeaturedAgents\/pdfs\/320846BatracylinShortPKAbstract.pdf."},{"key":"bibr13-0192623314548766","volume-title":"Guide for the Care and Use of Laboratory Animals","author":"National Research Council","year":"1996","edition":"7"},{"key":"bibr14-0192623314548766","doi-asserted-by":"publisher","DOI":"10.1007\/BF00175391"},{"key":"bibr15-0192623314548766","doi-asserted-by":"publisher","DOI":"10.4061\/2010\/920161"},{"key":"bibr16-0192623314548766","doi-asserted-by":"publisher","DOI":"10.3892\/ijo_00000311"},{"key":"bibr17-0192623314548766","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-0804"},{"key":"bibr18-0192623314548766","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-60327-409-8_18"},{"key":"bibr19-0192623314548766","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.13.9390"},{"key":"bibr20-0192623314548766","doi-asserted-by":"publisher","DOI":"10.1023\/A:1007692503817"}],"container-title":["Toxicologic Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0192623314548766","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/0192623314548766","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0192623314548766","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T16:36:33Z","timestamp":1777653393000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/0192623314548766"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,10,1]]},"references-count":21,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2015,6]]}},"alternative-id":["10.1177\/0192623314548766"],"URL":"https:\/\/doi.org\/10.1177\/0192623314548766","relation":{},"ISSN":["0192-6233","1533-1601"],"issn-type":[{"value":"0192-6233","type":"print"},{"value":"1533-1601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,10,1]]}}}