Related Experiment Video
Updated: Aug 13, 2026
Quantification of three DNA Lesions by Mass Spectrometry and Assessment of Their Levels in Tissues of Mice Exposed to Ambient Fine Particulate Matter
Published on: May 29, 2019
Molecular biomarkers of oxidative stress associated with bromate carcinogenicity
Don Delker1, Gary Hatch, James Allen
1Environmental Carcinogenesis Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA. delker.don@epa.gov
Abstract:
Potassium bromate (KBrO3) is a chemical oxidizing agent found in drinking water as a disinfection byproduct of surface water ozonation. Chronic exposures to KBrO3 cause renal cell tumors in rats, hamsters and mice and thyroid and testicular mesothelial tumors in rats. Experimental evidence indicates that bromate mediates toxicological effects via the induction of oxidative stress. To investigate the contribution of oxidative stress in KBrO3-induced cancer, male F344 rats were administered KBrO3 in their drinking water at multiple concentrations for 2-100 weeks. Gene expression analyses were performed on kidney, thyroid and mesothelial cell RNA. Families of mRNA transcripts differentially expressed with respect to bromate treatment included multiple cancer, cell death, ion transport and oxidative stress genes. Multiple glutathione metabolism genes were up-regulated in kidney following carcinogenic (400 mg/L) but not non-carcinogenic (20 mg/L) bromate exposures. 8-Oxodeoxyguanosine glycosylase (Ogg1) mRNA was up-regulated in response to bromate treatment in kidney but not thyroid. A dramatic decrease in global gene expression changes was observed following 1mg/L compared to 20 mg/L bromate exposures. In a separate study oxygen-18 (18O) labeled KBrO3 was administered to male rats by oral gavage and tissues were analyzed for 18O deposition. Tissue enrichment of 18O was observed at 5 and 24 h post-KBr18O3 exposure with the highest enrichment occurring in the liver followed by the kidney, thyroid and testes. The kidney dose response observed was biphasic showing similar statistical increases in 18O deposition between 0.25 and 50 mg/L (equivalent dose) KBr18O3 followed by a much greater increase above 50 mg/L. These results suggest that carcinogenic doses of potassium bromate require attainment of a threshold at which oxidation of tissues occurs and that gene expression profiles may be predictive of these physiological changes in renal homeostasis.
Insights
Potassium bromate (KBrO3) causes cancer by inducing oxidative stress. Carcinogenic doses require a threshold for tissue oxidation, with gene expression changes predicting these effects.
Area of Science:
- Environmental Toxicology
- Carcinogenesis
- Molecular Biology
Background:
- Potassium bromate (KBrO3) is a disinfection byproduct linked to cancer in animal studies.
- Bromate's toxicity is associated with oxidative stress induction.
- Understanding bromate's carcinogenic mechanisms is crucial for public health.
Purpose of the Study:
- To investigate the role of oxidative stress in potassium bromate-induced carcinogenesis.
- To analyze gene expression changes in response to bromate exposure in target organs.
- To determine the dose-response relationship for bromate deposition and its potential threshold effect.
Main Methods:
- Male F344 rats were exposed to various KBrO3 concentrations in drinking water for 2-100 weeks.
- Gene expression analysis (mRNA) was performed on kidney, thyroid, and mesothelial cells.
- Oxygen-18 labeled KBrO3 was administered to assess tissue deposition and dose-response.
Main Results:
- KBrO3 exposure altered expression of genes involved in cancer, cell death, ion transport, and oxidative stress.
- Glutathione metabolism and Ogg1 mRNA were upregulated in kidneys at carcinogenic doses.
- Tissue 18O enrichment showed a biphasic dose-response in kidneys, indicating a threshold for oxidation.
Conclusions:
- Carcinogenic potassium bromate doses necessitate reaching an oxidation threshold in tissues.
- Gene expression profiling can predict physiological changes related to bromate exposure and renal homeostasis.
- Oxidative stress is a key mediator in potassium bromate-induced toxicity and carcinogenicity.
