Understanding Health Consequences of Metals Exposure

There are numerous health effects that arise from exposure to metals.  Arsenic and uranium naturally occur in the environment and individuals are commonly exposed to these metals by inhalation and ingestion. This study will address mechanisms of potential health effects encountered by individuals exposed to arsenic and uranium through proximity to abandoned mines, geological deposits and the presence of arsenic in groundwater/ drinking water. Some of the health effects of arsenic are due to disruption of zinc finger proteins including DNA repair proteins such as Poly(ADP-ribose)polymerase-1 (PARP-1). There is some evidence that uranium may share this same mechanism of action. It is known that arsenic inhibits PARP-1 activity as well as contributing to oxidative DNA damage. Furthermore, arsenic and UV are synergistic in causing DNA damage, therefore potentially increasing the risk of certain types of cancer. Our lab is examining the effects of arsenic on human keratinocytes and the changes in expression of selected DNA repair proteins in a concentration and time dependant manner.  Using similar techniques, we plan to study the effects of uranium on DNA repair processes and potential disruption of zinc finger proteins.  While previous research suggests that uranium is genotoxic, it’s mechanism of action remains unknown.  Investigations on the mechanism of zinc finger disruption by carcinogenic metals are important because zinc can reverse the effects of arsenic in target proteins and cells.  If uranium acts through a similar mechanism, it is possible that zinc may provide a strategy to reduce toxicity in exposed populations.