Jun Nakamura, Ph.D., D.V.M., James Swenberg, Ph.D., D.V.M
University of North Carolina at Chapel Hill
NIEHS grantees identified DNA repair pathways that help cells tolerate small amounts of hexavalent chromium, a contaminant found at hazardous waste sites across the U.S., which is also a public health concern in drinking water.
Although inhaled hexavalent chromium is classified as a known human carcinogen, whether hexavalent chromium can cause cancer through ingestion is still open to debate. To investigate this, researchers analyzed how cells respond to hexavalent chromium by examining DNA damage response. They screened a variety of cells with different gene mutations to see which DNA repair genes and pathways are necessary for cells to survive exposure to hexavalent chromium.
The researchers found that DNA repair pathways are critical for cells to tolerate DNA damage caused by trace amounts of hexavalent chromium. They also identified four key components of DNA repair proteins that are responsible for rescuing cells from DNA damage.
They discovered that DNA damage was dependent on both the level of hexavalent chromium and the length of exposure. The team reported a 300-fold decrease in DNA damage response when the exposure to hexavalent chromium was shortened from 3 days to 10 minutes. Hexavalent chromium moves quickly through the digestive tract of animals that drink contaminated water. This could explain why previous studies in rodents have shown that hexavalent chromium ingestion is only carcinogenic at very high concentrations.
Citation: Tian X, Patel K, Ridpath JR, Chen Y, Zhou YH, Neo D, Clement J, Takata M, Takeda S, Sale J, Wright FA, Swenberg JA, Nakamura J. 2016. Homologous recombination and translesion DNA synthesis play critical roles on tolerating DNA damage caused by trace levels of hexavalent chromium. PLoS One 11(12):e0167503.