Abstract

Urothelial carcinoma (UCC) develops in both humans and dogs and tracks to regions of high industrial activity. We hypothesize that dogs with UCC may act as sentinels for human urothelial carcinogen exposures. The aim of this pilot study was to determine whether healthy people and dogs in the same households share urinary exposures to potentially mutagenic chemical carcinogens. We measured urinary concentrations of acrolein (as its metabolite 3-HPMA), arsenic species, 4-aminobiphenyl, and 4-chlorophenol (a metabolite of the phenoxyherbicide 2,4-D) in healthy dogs and their owners. We assessed possible chemical sources through questionnaires and screened for urothelial DNA damage using the micronucleus assay. Biomarkers of urinary exposure to acrolein, arsenic, and 4-chlorophenol were found in the urine of 42 pet dogs and 42 owners, with 4-aminobiphenyl detected sporadically. Creatinine-adjusted urinary chemical concentrations were significantly higher, by 2.8- to 6.2-fold, in dogs compared to humans. Correlations were found for 3-HPMA (r = 0.32, P = 0.04) and monomethylarsonic acid (r = 0.37, P = 0.02) between people and their dogs. Voided urothelial cell yields were inadequate to quantify DNA damage, and questionnaires did not reveal significant associations with urinary chemical concentrations. Healthy humans and pet dogs have shared urinary exposures to known mutagenic chemicals, with significantly higher levels in dogs. Higher urinary exposures to acrolein and arsenic in dogs correlate to higher exposures in their owners. Follow-up studies will assess the mutagenic potential of these levels in vitro and measure these biomarkers in owners of dogs with UCC.

Highlights

  • Urothelial carcinoma (UCC) develops in both humans and dogs and tracks to regions of high industrial activity

  • Urine creatinine was higher in dogs compared to humans, as expected based on higher urine concentrating ability in dogs compared to humans [26,27]

  • Biomarkers of urinary exposure to the mutagenic chemicals acrolein, inorganic arsenic, 4-chlorophenol, and, to a lesser extent, 4-aminobiphenyl were found in the urine of healthy pet dogs and their owners, and urinary exposures were significantly higher in dogs

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Summary

Introduction

Urothelial carcinoma (UCC) develops in both humans and dogs and tracks to regions of high industrial activity. We hypothesize that dogs with UCC may act as sentinels for human urothelial carcinogen exposures The aim of this pilot study was to determine whether healthy people and dogs in the same households share urinary exposures to potentially mutagenic chemical carcinogens. Bladder cancer in humans is associated with regions of higher industrial activity, even among people in non-industrial occupations [5,8]. This may result from chronic low-grade exposures to known bladder carcinogens such as arsenic (found in contaminated ground water and air pollution), acrolein (found in air pollution and processed heat-treated foods), and 4-aminobiphenyl (found in cooking fumes and other sources of air pollution) [9,10]. The time from environmental exposure to cancer development can be decades [5], and the median age of onset of urothelial carcinoma is 67 years [11]

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