Table 2_Genotoxic exposures to volatile organic compounds in golden retrievers with and without multicentric lymphoma.docx

Canine multicentric lymphoma is a common cancer in dogs with poor long-term outcomes. In people, non-Hodgkin lymphoma is associated with volatile organic compounds (VOCs), but this risk is not clear for lymphoma in dogs. The objective of this study was to investigate whether dogs with lymphoma were more likely to be exposed to DNA-damaging concentrations of VOCs compared to unaffected controls. We measured stable urinary metabolites of the VOCs benzene, xylene, and 1,3-butadiene in golden retrievers with multicentric lymphoma and matched unaffected controls at 2 time points: the time of diagnosis and 1 year prior. We then determined genotoxic effects for xylene and bioactivated benzene in canine peripheral blood mononuclear cells (PBMCs) in vitro and compared them to in vivo blood concentrations estimated using reverse dosimetry. All dogs had detectible urinary concentrations of the benzene metabolites PHMA and MUCA, the xylene metabolite 34MHA, and 1,3-butadiene metabolites MHB3 and DHBM, with no differences between cases and controls. Six of 30 cases and none of 30 controls were positive for urinary cotinine, a marker of secondhand smoke (p = 0.028), but urinary VOC concentrations did not differ between cotinine-positive and -negative dogs. Bioactivated benzene was genotoxic to canine PBMCs at ≥ 10 uM and xylene was genotoxic at ≥ 0.5 uM. Estimated blood benzene and xylene concentrations reached genotoxic exposures in most dogs. These results support a recommendation to reduce VOC exposures in pet dogs, for example by using activated carbon indoor air filtration units rated for VOC removal.