PgmNr W4081: Investigating DNA damage response pathways after exposure to various heavy metals in C. elegans.

Authors:
J. Hall; S. Koga; S. Parag; K. Campbell; M. McMurray


Institutes
Lincoln Memorial University, Harrogate, TN.


Keyword: Stress response

Abstract:

A major route of exposure to various heavy metals is through contaminated soil and water. Research has shown that these substances play roles in the induction of various diseases such as cancer, neurodegeneration and birth defects. In the cell, proteins such as metallothioneins respond to heavy metal exposure and chelate the metal to prevent cellular damage. However, little is known about the cellular response in regards to DNA damage after heavy metal exposure. To provide a better understanding of this cellular response, the induction of both cell cycle arrest and apoptosis were investigated after exposure to copper, cadmium, iron, lead, nickel and silver in the nematode C. elegans. Growth assays were conducted to determine EC10 and EC50 concentrations which were utilized to determine the DNA damage response pathway, apoptosis and/or cell cycle arrest, being induced upon exposure. Apoptosis and cell cycle arrest were observed in the germline after 24 hour exposure to the heavy metal. Apoptosis in the germline was induced in response to both concentrations of nickel. Additionally, apoptosis was also observed in the early embryo after nickel exposure suggesting an effect on reproduction rates. Both iron and silver exposure resulted in a slight increase in apoptosis at the EC50 concentration. Apoptosis and cell cycle assays for all metals tested will allow us to better understand the damage being caused by the metal exposure as well as mechanisms induced by the cell in response to exposure.