2017 Participants
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NAME: Thomas Whitlow

Development of a Novel Cellular and Molecular based Toxicology Assay using RTgill-W1 Cell Cultures Exposed to High Concentrations of Manganese (II).  

Manganese (Mn) is an essential nutrient to most complex life. In high concentrations, manganese proves to be a damaging, if not deadly force to any life exposed for prolonged amounts of time. There has been a fair amount of research in mammals regarding the effects of manganese, finding that manganese acts as a neurotoxin when in high concentrations and gives rise to parkinsonian-like symptoms. While the effects of manganese are known in mammals, the mechanisms of how manganese affects DNA are still poorly characterized. There is a surprisingly small number of studies done on manganese toxicity in fish, as well. Manganese was selected as the target heavy metal due to its prevalence in streams around the region from mountain top removal and other types of mining. In earlier years, there was little worry for manganese in bodies of water, due to a process by which iron was used to precipitate heavy concentrations of manganese out of water. Recently, however, there has been findings that manganese may have negative effects at lower concentrations. It is currently believed that, as well as a neurotoxin, manganese causes DNA damage (genotoxin), and may be linked to the poly(ADP- ribose) polymerase-1, or PARP-1, protein, due to its indirect role in apoptosis via mitochondrial pathways. Manganese reacts in the cell to inhibit PARP-1 activity, which plays a major role in DNA repair. In higher concentrations of manganese, PARP-1 is phosphorylated and thus rendered inactive, leading the cell to apoptosis due to extensive DNA damage. Trout are common in Appalachia, and may be effected by the presence of manganese due to runoff from the local mines and regional chemical and coal plants. To better understand the mechanisms and effects of manganese on fish, the rainbow trout cell line RTgill-W1 will be exposed to specific concentrations to test for cell death, DNA damage, PARP-1 protein phosphorylation, and effects on mitochondrial membrane potential.

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