Evidence of epigenetic factors in the response of human lung fibroblasts from male and female cell sources during exposure to heavy metals and World Trade Center 9-11 particulate matter

Several chronic health conditions have been associated with first- responders, cleaning workers, and residents of the area affected by the World Trade Center (WTC) tragedy on September 11, 2001. Chronic pulmonary diseases and cancer are among the ailments of those who inhaled WTC particulate matter. Significant differences between males and females in the epidemiological response to this toxic dust have never been completely analyzed. These preliminary in vitro studies attempt to demonstrate that cell culture can be used to help uncover different responses between males and females. Historically, there has been a prevalent misconception in scientific research that suggests there is no difference in mammalian physiology between cell sexes. However, over the past five years this notion has been increasingly challenged by researchers. This experiment will use both cells from male and female sources, to determine sensitivity to WTC dust and several heavy metals identified in this toxic dust. Promega CellTiter 96® Aqueous One Solution Cell Proliferation Assay was used to determine the difference in proliferation of male MRC-5 lung fibroblast cells with female WI-38 lung fibroblast cells. These cells were maintained in normal conditions before controlled exposure to either dust from WTC and several heavy metals. Metals of interest identified in this dust include copper, manganese, and lead. WI-38 cells appear to be more sensitive to exposure to this toxic dust than MRC-5. Copper was seen to be equally involved in decrease of cellular proliferation in both cell strains and the sensitivity to damage was significant. Remarkably small amounts of lead were also noted in rapid decrease in normal cell proliferation. The WI-38 cells also show further proliferation decrease than the MRC-5 cells when exposed to manganese. Further studies should focus on the specific cellular organelle exposed to damage. Future studies will analyze the different levels of the GTPase protein involved in the mitogenic pathway, as well as nitrate stress. Based on the preliminary proliferation work, further studies will continue to look at male female differences.