{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T13:54:37Z","timestamp":1789221277922,"version":"build-2803163510"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T00:00:00Z","timestamp":1766448000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Urothelial carcinoma (UC) in pet dogs closely resembles human muscle-invasive UC, which is associated with environmental chemical carcinogens. The aim of this study was to determine whether urinary concentrations of the bladder carcinogens acrolein, inorganic arsenic, and 2,6-dimethylaniline (2,6-DMA) reach genotoxic concentrations in pet dogs with and without UC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We first established thresholds for DNA damage from these chemicals using a novel\n                      <jats:italic>in vitro<\/jats:italic>\n                      organoid model. Healthy canine urinary bladder organoids were exposed to acrolein, sodium arsenite, and 2,6-DMA\n                      <jats:italic>in vitro<\/jats:italic>\n                      and we used the alkaline CometChip assay without and with the enzyme Fpg (\n                      <jats:italic>formamidopyrimidine [fapy]-DNA glycosylase<\/jats:italic>\n                      ) to measure DNA strand breaks and oxidative DNA damage.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      For acrolein, we found a genotoxic threshold of 20 uM for combined DNA strand breaks and oxidative DNA damage. These findings suggest potentially genotoxic urinary acrolein exposures in 20% of pet dogs (15 of 74) previously surveyed, with no differences between cases and controls. For inorganic arsenic, we observed genotoxicity at 20 uM in canine organoids; none of 74 pet dogs reached this urinary concentration when assayed at a single time point. For 2,6-DMA, the genotoxic threshold was 0.01 uM for combined DNA strand breaks and oxidative DNA damage. Among dogs previously surveyed, 8% of UC cases (3 of 37) and none of 36 controls reached this threshold (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.07).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Acrolein and 2,6-DMA could reach genotoxic urinary concentrations after household exposures in some pet dogs, and the role of 2,6-DMA in canine bladder cancer risk deserves assessment in a larger sample size.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fvets.2025.1702980","type":"journal-article","created":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T13:32:32Z","timestamp":1766496752000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Urothelial genotoxicity of household chemicals in healthy canine urinary bladder organoids relative to observed urinary exposures in pet dogs"],"prefix":"10.3389","volume":"12","author":[{"given":"Hannah M.","family":"Peterson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Zdyrski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Allenspach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan P.","family":"Mochel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren A.","family":"Trepanier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,23]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1093\/ilar\/ilu018","article-title":"Urinary bladder cancer in dogs, a 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