{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T10:24:50Z","timestamp":1777717490547,"version":"3.51.4"},"reference-count":23,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2006,3,1]],"date-time":"2006-03-01T00:00:00Z","timestamp":1141171200000},"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":["Int J Toxicol"],"published-print":{"date-parts":[[2006,3]]},"abstract":"<jats:p>4\u2032-Thio- \u03b2-d-arabinofuranosylcytosine (OSI-7836) is a nucleoside analogue with structural similarity to gemcitabine and cytarabine (ara-C). Myelosuppression, reversible transaminase elevations, and flu-like symptoms are common side effects associated with human use of gemcitabine and ara-C. Fatigue is also associated with the use of gemcitabine and OSI-7836 in humans. To better understand the toxicity of OSI-7836, subchronic studies were conducted in dogs. OSI-7836 was administered on days 1 and 8 or on days 1, 2, and 3 of a 21-day dose regimen. These schedules attempted to match clinical trial dosing regimens. Routine toxicity study end points demonstrated that OSI-7836 was primarily cytotoxic to the gastrointestinal tract, bone marrow, and testes; the myelotoxicity was mild and reversible. Plasma pharmacokinetics were dose-linear with an elimination half-life of 2.2 h. Follow-up single dose experiments in dogs assessed drug effects on lymphocyte subpopulations and on adrenal and thyroid function. Populations of T and B cells were equally reduced following OSI-7836 administration. There were no adverse effects on thyroid function, but there were marked reductions in circulating cortisol and adrenocorticotropic hormone concentrations suggesting a centrally mediated impairment of the hypothalamic-pituitary-adrenal axis. These findings show a toxicological profile with OSI-7836 similar to other nucleoside analogues and suggest that the beagle is a model for studying one possible cause of OSI-7836-related fatigue, impaired function of the hypothalamic-pituitary-adrenal axis.<\/jats:p>","DOI":"10.1080\/10915810600605898","type":"journal-article","created":{"date-parts":[[2006,4,4]],"date-time":"2006-04-04T19:39:00Z","timestamp":1144179540000},"page":"119-126","source":"Crossref","is-referenced-by-count":4,"title":["Safety Assessment of 4\u2032-Thio-\n                    <i>\u03b2<\/i>\n                    -\n                    <scp>d<\/scp>\n                    -Arabinofuranosylcytosine in the Beagle Dog Suggests a Drug-Induced Centrally Mediated Effect on the Hypothalamic-Pituitary-Adrenal Axis"],"prefix":"10.1177","volume":"25","author":[{"given":"Dorothy B.","family":"Colagiovanni","sequence":"first","affiliation":[{"name":"OSI Pharmaceuticals, Inc., Boulder, Colorado, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel W.","family":"Drolet","sequence":"additional","affiliation":[{"name":"OSI Pharmaceuticals, Inc., Boulder, Colorado, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Larry","family":"Dihel","sequence":"additional","affiliation":[{"name":"OSI Pharmaceuticals, Inc., Boulder, Colorado, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dennis J.","family":"Meyer","sequence":"additional","affiliation":[{"name":"OSI Pharmaceuticals, Inc., Boulder, Colorado, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen","family":"Hart","sequence":"additional","affiliation":[{"name":"OSI Pharmaceuticals, Inc., Boulder, Colorado, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie","family":"Wolf","sequence":"additional","affiliation":[{"name":"OSI Pharmaceuticals, Inc., Boulder, Colorado, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2006,3,1]]},"reference":[{"key":"b1-0250119","first-page":"965","volume":"43","author":"Blajeski AL","year":"2002","journal-title":"Proc. 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