NIEHS researchers and their collaborators recently found exposure to potassium bromate causes distinct changes in yeast DNA, and that footprints of the same changes, or mutations, are found in samples of human esophageal, stomach, and colorectal cancer. The study was published April 20 in the journal Nucleic Acids Research.

Potassium bromate is widely used in the U.S. baking industry to make dough rise higher in the oven and make it easier to handle. However, many countries in Europe and Asia have banned its use due to concerns that it may cause cancer.

Although there is no definitive evidence or studies showing potassium bromate causes cancer in humans, the current study provides another clue about human exposures to the oxidizing agent.

“The discovery that there are distinct changes in yeast DNA linked to potassium bromate exposure and these same mutational changes are also observed in digestive tract cancers raises a red flag,” said Paul Doetsch, Ph.D., deputy scientific director and senior investigator in the NIEHS Division of Intramural Research, who led the study.

“When you eat a pizza, you're going to be ingesting potassium bromate,” he explained. “When you eat other kinds of store-bought baked goods, there's a good possibility that you will be ingesting and exposing your digestive track to some level of potassium bromate.”

The research team also found the mutational signatures — or specific base pair changes within specific motifs of adjacent nucleotides in DNA — linked to potassium bromate are not seen with other redox stress agents.

Mutations mirror metabolic changes

Doetsch and NIEHS collaborators, including Natalya Degtyareva, Ph.D., Scott Gabel, Leszek Klimczak, Ph.D., and Geoffrey Mueller, Ph.D., also discovered other biological changes occurred when yeast cells were exposed to potassium bromate. They found changes in cellular metabolism, meaning the levels of certain metabolites or molecules changed as a result of chemical processes aimed at generating new molecules and breaking down others.

According to Doetsch, there is a distinct pattern of change in the metabolites the researchers measured. Moreover, the way that they changed — increased or decreased levels — could be seen as a signature of metabolite changes for potassium bromate exposure.

“These metabolic changes can be matched with the mutational signatures that they cause, and it clearly tells us how potassium bromate changes a cell’s metabolism, and how it damages the cell’s DNA, causes mutations, and in some cases ends up killing the cell,” Doetsch explained.

Some antioxidants increase toxicity

Antioxidants normally reduce disease-causing oxidative stress. For example, antioxidant-rich fruits and vegetables are recommended for this purpose. However, the researchers also found a certain class of antioxidants, specifically those that contain thiol, increase the cell death and the mutagenic effects of potassium bromate in humans.

“This was totally unexpected and shows that something that we thought was a good thing — to scavenge radicals and neutralize the effects of oxidative stress — actually had the opposite effect in the presence of potassium bromate,” Doetsch said.

Human consumption of thiol-containing antioxidants as a dietary supplement is prevalent, and antioxidants are sometimes used to supplement the diet of cancer patients.

“Our study clearly shows that you should be very careful about the decision to consume this style of antioxidants as a dietary supplement.” Doetsch explained.

He added, “If you were thinking of treating a cancer patient with antioxidants, and you knew of these untoward effects of certain redox stress agents with thiol-containing antioxidants, you might think twice about including thiol-containing antioxidants.”