There are plenty of potentially mutagenic agents that, individually and at very low levels, pose little threat to human health. Arsenic, estrogen—humans come into contact with these all the time.

But even at levels considered safe by Environmental Protection Agency, a combination of arsenic and estrogen exposure could be harmful, researchers at Texas Tech University have found.

Kamaleshwar Singh, Ph.D., and his colleagues treated human prostate cells with “safe” levels of arsenic, estrogen, and a combination of both once weekly for six months. They found that the cells exposed to both arsenic and estrogen were almost twice as likely to become cancerous than those that were not in contact with both agents.

“Science has looked at these chemicals, such as arsenic, and tested them in a lab to find the amounts that may cause cancer. But that’s just a single chemical in a single test. In the real world, we are getting exposed to many chemicals at once,” Dr. Singh said in a statement.

“Co-exposure was creating a greater impact,” he added. “That was one of the important findings of our study. The next thing we wanted to know is how these two chemicals are creating a greater effect.”

Justin Treas, Ph.D., a postdoc in Dr. Singh’s lab pinpointed the gene MLH1 as one target of the two agents. He said that the arsenic-estrogen combination halted MLH1, which plays a role in a cell’s self-destruct signaling once it has become damaged.

“With the lower dose not killing the cell, it’s causing damages that go under the cell’s radar,” Treas said. “We found when you have two compounds together, lower doses could be more serious problem.”

“Chronic exposure to arsenic, estrogen, and their combination causes increased growth and transformation in human prostate epithelial cells potentially by hypermethylation-mediated silencing of MLH1” was published online in The Prostate June 26.

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