Investigating the molecular mechanisms involved in the modulation of aryl hydrocarbon receptor (AhR)-regulated genes by environmental pollutants and contaminants, such heavy metals, at the activity, protein and mRNA levels in hepatic cell lines. Heavy metals such as mercury, lead and copper are of health concern because of the possibility of environmental contamination by both natural and man-made sources, and the impact that such contamination can have on human health.
Heavy metals and AhR ligands are common environmental co-contaminants of hazardous waste sites and are co-released from sources such as fossil fuel combustion and municipal waste incineration and as components of tobacco. Both AhR ligands and heavy metals are ranked highly as the most hazardous xenobiotics in the environment, prepared by Canadian Environmental Protection Act and the Agency for Toxic Substances and Disease Registry and the Environmental Protection Agency. The toxicity of AhR ligands is based on their bioactivation by CYP1A1 to yield mutagenic and carcinogenic intermediates. Environmental co-contamination of heavy metals with AhR ligands could affect the mutagenicity and carcinogenicity of these compounds.
My long-term objectives are to 1) understand the potential interaction between heavy metals and AhR ligands which are common in the environment on the regulation of AhR-regulated genes, and 2) investigate the effects of AhR ligand/metal mixtures on AhR ligands mutagenicity and carcinogenicity.