The goal of our hatch project is to determine how common man-made chemicals can impact cellular mechanisms that will increase cancer progression. Previous data from our demonstrates that exposure to a select polycyclic aromatic hydrocarbons (PAHs), tetrachlorodibenzo-p-dioxin (TCDD), changes the expression and activity of enzymes that are involved in cancer metastasis. To follow up on these data, we are now proposing to continue this work, focusing on emerging PAHs of concern, the brominated flame retardant TBBPA (tetrabromobisphenol-A) and the plastic BPA (bisphenol-A). Both of these chemicals are extensively used, and both have been detected in human tissues, demonstrating human exposure. To examine the effect of these chemicals on matrix metabolism, we are using the developing zebrafish, as the pathways important for development are found to be pivotal to cancer progression. Our preliminary data indicate that exposure to TBBPA results in abnormal development and changes in expression of enzymes involved in cancer metastasis. Furthermore, our data indicate that metabolism of this compound by microbes in the environment reduces their toxicity and their ability to increase the expression of these enzymes. Interestingly, though BPA does have a negative effect on the developing embryo, microbial metabolism increases the toxicity of this compound. Therefore, understanding how microbial metabolism of common environmental chemicals alters toxicity and the ability to activate pathways critical for cancer progression will have a significant effect on the risk assessment of these compounds. Furthermore, discovering whether these metabolic transformations can be mediated by the gut microflora is critical to determining the actual exposure in humans. Therefore, the aims of this proposal are to examine the effect of these compounds and their metabolites on pathways critical for cancer progression, and to determine whether microbes in the mammalian gut can metabolize these compounds. The impacts of this project reach beyond the potential change in risk assessment for TBBPA and BPA. As project is one of the first to examine the potential link between microbial metabolism and toxicity, and it could alter the risk assessment of similar compounds, and potentially change some of the required protocols for determining the ultimate toxicity of man-made chemicals. Our latest article on BPA (McCormick et al, 2011), has generated a considerable amount of interest in the field and in the mainstream media. The results from these studies will be presented at national meetings, and in peer reviewed journals. In addition, if appropriate, we will present these findings to the Food and Drug Administration (FDA).
|Effective start/end date||10/1/11 → 9/30/16|
- National Institute of Food and Agriculture (National Institute of Food and Agriculture (NIFA))