Superfund Research Program
PCBs: Metabolism, Genotoxicity and Gene Expression in vivo
Project Leader: Larry W. Robertson
Grant Number: P42ES013661
Funding Period: 2006-2020
Project Summary (2015-2020)
Polychlorinated biphenyls (PCBs) are a group of 209 individual congeners that differ widely in their toxic effects and mechanisms of toxicity. Most research has focused on the effects of higher chlorinated PCBs because they bioaccumulate. However, exposure to lower chlorinated, more volatile biphenyls through contaminated indoor and outdoor air can be very high for some populations. These airborne PCBs are readily bio activated and exhibit their own, distinct spectra of toxic effects. Project researchers are investigating the hypothesize that airborne PCBs can bring about inappropriate changes in the redox status and macromolecule function of cells and tissues through different, distinct mechanisms, leading to detrimental effects on health, and that through understanding these mechanisms, strategies to ameliorate these health effects can be designed.
The discoveries project researchers have made in the previous funding periods have fundamentally changed views on the toxicity of PCBs. Their data provided key information for the reclassification of PCBs to Group 1, human carcinogens, by the International Agency of Research on Cancer (IARC). Their new discoveries supply the foundation for this research. The researchers are studying PCBs occurring most often in air, and their metabolites, to:
- Provide an in-depth analysis of the disruptions in the redox networks, redox environment, and basic energy metabolism-respiration of cells and tissues upon exposure
- Identify the active congeners/metabolites to elucidate structure-activity relationships of (geno)toxicity, ranking them in importance and potential consequences to human health
- Identify sensitive target tissues, analyze organ specificity, and determine threshold levels and toxicity
- Examine the potential of dietary approaches to prevent or ameliorate toxicity
- Assess human mother-child samples with known PCB and metabolite body burdens to develop biomarkers of exposure and effects, and to identify potential susceptible subpopulations
The project is leading to new knowledge that will enable data-driven risk assessment, as well as chemoprotective and therapeutic methods to prevent or ameliorate the detrimental effects of PCBs and other toxicants. The project's approach is integrative and diverse, ranging from fundamental physical chemistry, to detailed analysis of effects at the â€˜molecule per cell' level, to dissection of the interactions between different congeners of PCBs, effects of micronutrients, and analysis of human samples to determine consequences of exposure. With a clear focus on these goals, this research program meets the mission of the Superfund Research Program exceptionally well, pushing the boundaries of science with a view to the future for effective hazard management and health protection.