John Pierce Wise, Ph.D.
University of Louisville
NIEHS grantees showed that exposure to hexavalent chromium can lead to changes to genetic information in human lung cells. Hexavalent chromium is a known lung carcinogen, but the mechanism by which it causes cancer is not well understood. In human lung cells exposed to hexavalent chromium, the researchers observed permanent and heritable changes in DNA molecules that carry genetic information, known as chromosomes, as well as problems in DNA repair.
The researchers exposed lung cells to hexavalent chromium for three 24-hour periods, each about a month apart. After each treatment, they seeded cells onto new plates to regrow. Each generation of cells was tested for changes to chromosomes and DNA repair capacity.
The study provided evidence for the first time that hexavalent chromium induced chromosome translocations, or abnormal arrangements of chromosomes. They also found that exposure to hexavalent chromium inhibited DNA repair. Both the chromosome translocations and the DNA repair inhibition persisted after exposure ceased and both were heritable at the cellular level.
According to the authors, these chromosome imbalances likely lead to preferential selection and survival of abnormal cells, which may provide a growth advantage for cancer cells.
Citation: Wise SS, Aboueissa AE, Martino J, Wise JP Sr. 2018. Hexavalent chromium-induced chromosome instability drives permanent and heritable numerical and structural changes and a DNA repair-deficient phenotype. Cancer Res 78(15):4203−4214.