Aryl hydrocarbon receptor mediated responses to environmental toxicants

A group of environmental pollutants, which may pose a potential health risk to humans, is the polycyclic aromatic hydrocarbons (PAHs). PAHs are found in urban air and occupational environments, and a very large part of the population is exposed to these c ompounds. An important source of PAH exposure is tobacco smoke. Chronic exposure to these pollutants has been linked to the development of diseases such as cancer, COPD, cardiovascular diseases, and allergic disorders including asthma, dermatitis, rhiniti s and bronchitis. It is therefore important to identify molecular mechanisms and processes that are involved in mediating their adverse health effects. In the cell, PAHs bind to the aryl hydrocarbon receptor (AHR), and this process mediates the toxic effe cts of the compounds. After binding, the AHR becomes an active regulator of many genes. Among these are genes that are involved in the biotransformation of the PAHs and genes involved in inflammatory processes. There is evidence that other intracellular r eceptors, such as the receptors for the female hormone estrogen, may modulate the gene regulatory activity of the AHR. It is not clear, however, exactly how these interactions take place and what other cellular factors are involved. In the present project , we will study interactions between estrogen receptors and the AHR. In human lung cells, we will study the effect of knocking down these receptors on gene regulation mediated by AHR. We will measure the cells capacity to biotransform PAHs in the presence and absence of estrogen receptor, and the effect on genes that are involved in inflammation. Increased knowledge on these processes is needed in order to answer important questions concerning for example if the susceptibility to toxic effects of PAH diff er between women and men.