Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Your Environment. Your Health.

University of Iowa

Superfund Research Program

PCBs: Metabolism, Genotoxicity and Gene Expression in vivo

Project Leader: Larry W. Robertson
Co-Investigators: Garry R. Buettner, Howard P. Glauert (University of Kentucky), Wanda M. Haschek-Hock (University of Illinois at Urbana-Champaign), Gabriele Ludewig
Grant Number: P42ES013661
Funding Period: 2006-2020

Learn More About the Grantee

Visit the grantee's eNewsletter page Visit the grantee's eNewsletter page Visit the grantee's Twitter page

Project Summary (2006-2010)

Airborne PCBs are those that have higher vapor pressures, lower chlorination, and should be substrates for metabolic activation. Dr. Robertson's team hypothesizes that the lower halogenated biphenyls are activated by hepatic enzymes to oxygenated species that are electrophilic and bind to proteins and DMA. Preliminary data indeed show that PCBs are metabolized to electrophiles and free radicals that bind to cellular targets and that the metabolism of PCBs produces reactive oxygen species, resulting in DMA strand breaks and 8-oxodeoxyguanosine formation in DMA and that a quinone/semiquinone may be a/the major metabolite involved in these effects. Employing the Solt-Farber initiation-selection protocol, the researchers also identified several lower chlorinated biphenyls as initiators of hepatocarcinogenesis in the rat. The goals of this study are to: 1) determine the initiating potential of airborne, semi-volatile PCBs and to analyze the structural and metabolic requirements needed for carcinogenic potency, 2) analyze for oncogene mutations and karyoptypic changes during PCB carcinogenesis in the Solt-Farber experiments, 3) investigate the types of genotypic damage induced by PCBs and their metabolites in vitro, in cells in culture, and in vivo, 4) examine the ease of formation and the reactivity of PCB-derived semiquinone radicals, and 5) determine the biologic effects and the influence of Route of Exposure (IP vs. inhalation) of airborne PCBs (a typical "air mixture" of PCBs, or single PCB congeners, or hydroxy-PCBs) on specific changes in expression of xenobiotic-metabolizing enzymes, antioxidant enzymes or redox indicators in the rat. Jointly these studies may explain why some PCBs are activated to genotoxins, while others are not, which target genes are involved, the nature of the DNA lesions, and the mutations that ensue. These data may also provide clues about whether nutritional or other interventions are warranted to protect highly exposed humans. These mechanistic and susceptibility issues will form a basis for the quantitative human health risk assessment for these important Superfund chemicals, arising from multiple sources.

Back
to Top