Diverse Toxicants Share Mechanism Of Action

Chemically diverse toxicants in the environment cause oxidative stress on human cells in myriad ways. That makes toxicity predictions for new chemicals a challenge. Now, researchers at the University of Rochester Medical Center have discovered that these harmful effects converge on a single protein pathway involved in cell division (PLoS Biol., DOI: 10.1371/journal.pbio.0050035).

The identification of this common pathway sets the stage for developing a diagnostic test to evaluate tens of thousands of chemicals for which little or no toxicological information exists, senior author Mark Noble suggests.

The research team initially tested methylmercury, lead, and the herbicide paraquat and found that the toxic effects of these chemicals activate a protein called Fyn in progenitor cells. This process eventually leads to reduced cell division. Noble's lab now has tested more than a dozen other agents, ranging from pesticides to chemotherapy agents. The researchers are finding that environmentally relevant concentrations of these chemicals also trigger Fyn. The result lends credence to the idea that this pathway could become the basis of sensors for toxicity resulting from toxic stress.