{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T15:51:21Z","timestamp":1770220281479,"version":"3.49.0"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,7,8]],"date-time":"2018-07-08T00:00:00Z","timestamp":1531008000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Veterinary Pharmacology Research Foundation"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Vet Comparative Oncology"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:p>The antineoplastic agent cyclophosphamide (CP) has dose\u2010limiting side effects including sterile haemorrhagic cystitis (SHC), bone marrow (BM) suppression and gastrointestinal (GI) toxicity in dogs. The metabolites acrolein and phosphoramide that mediate these toxicities are glutathione\u2010S\u2010transferase (GST) substrates, and low functioning GST alleles are associated with CP toxicity in humans. The aim of this study was to determine whether variants in 2 canine GST genes,<jats:italic>GSTT1<\/jats:italic>and<jats:italic>GSTT5<\/jats:italic>, were over\u2010represented in dogs that developed CP toxicity. Dogs undergoing pulse or metronomic CP chemotherapy were recruited (<jats:italic>n<\/jats:italic>\u2009=\u2009101) and genotyped for 6<jats:italic>GSTT1<\/jats:italic>polymorphisms and 1<jats:italic>GSTT5<\/jats:italic>6\u2010bp deletion that leads to non\u2010functional enzyme. Median cumulative CP dosages for dogs with SHC (1350\u2009mg\/m<jats:sup>2<\/jats:sup>) were significantly higher than for dogs with GI\/BM toxicity (871\u2009mg\/m<jats:sup>2<\/jats:sup>) or no toxicity (991\u2009mg\/m<jats:sup>2<\/jats:sup>;<jats:italic>P<\/jats:italic>\u2009=\u2009.0012). Dogs with SHC were more likely to have had metronomic (84.2%, 16 of 19 SHC cases) vs pulse (15.8%, 3 of 19 SHC cases) CP dosing (<jats:italic>P<\/jats:italic>\u2009&lt;\u2009.0001). All dogs with BM or GI toxicity (<jats:italic>n<\/jats:italic>\u2009=\u200930) had pulse chemotherapy.<jats:italic>GSTT1<\/jats:italic>and<jats:italic>GSTT5<\/jats:italic>variant allele frequencies were not significantly different in CP\u2010treated dogs with SHC or GI\/BM toxicity compared to dogs without documented adverse effects. Work is underway to identify which canine GSTs detoxify acrolein and phosphoramide, so that better tools are available to predict the risk of CP toxicity in dogs.<\/jats:p>","DOI":"10.1111\/vco.12411","type":"journal-article","created":{"date-parts":[[2018,7,9]],"date-time":"2018-07-09T02:23:27Z","timestamp":1531103007000},"page":"529-534","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Glutathione\u2010S\u2010transferase\u2010theta genotypes and the risk of cyclophosphamide toxicity in dogs"],"prefix":"10.1111","volume":"16","author":[{"given":"J.","family":"Ekena","sequence":"first","affiliation":[{"name":"Department of Medical Sciences School of Veterinary Medicine, University of Wisconsin\u2010Madison Madison Wisconsin"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Wood","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences School of Veterinary Medicine, University of Wisconsin\u2010Madison Madison Wisconsin"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Manchester","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences School of Veterinary Medicine, University of Wisconsin\u2010Madison Madison Wisconsin"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Chun","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences School of Veterinary Medicine, University of Wisconsin\u2010Madison Madison Wisconsin"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8585-7350","authenticated-orcid":false,"given":"L. 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