Modification of the epigenetic landscape by arsenic

Modification of the epigenetic landscape by arsenic

Relevance to SWEHSC: 
The absence of mechanistic explanations for the increased risk of cancers from arsenic exposure in humans confounds regulators and hinders progress in mitigation of risk in exposed populations. A growing body of data suggests that one key mechanism of arsenic may be the perturbation of epigenetic gene regulation.
Cluster of Efforts: 
Investigators/Funding: Futscher (RFG1), Gandolfi (RFG1), Klimecki (RFG1, IHSFC) NCI/CA015159

                   

Milestones: 
  • This grant, awarded under a joint NIEHS/NCI RFA, studies the epigenetic status of both human cell lines exposed to arsenic, as well as exfoliated bladder cells from exposed human study participants exposed to arsenic at defined low and high levels of arsenic exposure. NCI/CA015159
  • Arsenic exposure to UROtsa cell lines alters the levels of siRNA species with defined involvement in epigenetic gene regulation
  • Genome-wide measurement of epigenetic marks on DNA from exfoliated bladder cells from arsenic-exposed people, analyzed by principal component analysis, result in segregation of the samples into clusters of low exposure and high exposure individuals, suggesting that the epigenetic landscape is modified by arsenic and that epigenetic signatures may be promising biomarkers of arsenic exposure and disease. NIEHS/ES004940, NCI/CA015159