Arsenic and Line-1 Disrupt Developmental Epithelial to Mesenchymal Transition: Implications for Cardiac Morphogenesis

Chronic exposure to arsenic is linked to increased risk for cancers of the lung, kidney, bladder, and liver. Non-cancerous disease endpoints such as atherosclerosis, birth defects, metabolic syndrome and hypertension are also associated with arsenic exposure. Many of the organ systems impacted by arsenic require epithelial to mesenchymal cell transition (EMT) to establish and maintain tissue homeostasis. For example, developmental EMT contributes to lung, neural tube and heart morphogenesis. As such, disruption of EMT programming by arsenic can result in birth defects and predispose to diseases later in life. The mechanisms by which arsenic disrupts EMT is not known. Long interspersed element 1 (LINE-1 or L1) is a retrotransposon of the human and mouse genomes, and recently linked to conotruncal heart defects. Such defects arise from malformation of the outflow tract of the embryonic heart through altered EMT. In the present study, we discovered induction of Line-1 by arsenic and investigated whether Line...