ORIGINAL RESEARCH article
Front. Vet. Sci.
Sec. Veterinary Pharmacology and Toxicology
Urothelial genotoxicity of household chemicals in healthy canine urinary bladder organoids relative to observed urinary exposures in pet dogs
Provisionally accepted
- 1University of Wisconsin-Madison, Madison, United States
- 2University of Georgia, Athens, United States
- 3Iowa State University of Science and Technology, Ames, United States
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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. We first established thresholds for DNA damage from these chemicals using a novel in vitro organoid model. We exposed healthy canine urinary bladder organoids to acrolein, sodium arsenite and 2,6-DMA in vitro and used the alkaline CometChip assay without and with the enzyme Fpg (formamidopyrimidine [fapy]-DNA glycosylase) to measure DNA strand breaks and oxidative DNA damage. 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 (P = 0.07). 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.
Keywords: Comet Assay, DNA Damage, Bladder cancer, Aromatic amines, Arsenic, Acrolein
Received: 10 Sep 2025; Accepted: 24 Nov 2025.
Copyright: © 2025 Peterson, Zdyrski, Allenspach, Mochel and Trepanier. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Lauren A Trepanier, latrepanier@vetmed.wisc.edu
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