Superfund Research Program
Biomarkers of Exposure versus Effect: Improving the Scientific Basis for Risk Assessment
Project Leader: James A. Swenberg
Grant Number: P42ES005948
Funding Period: 1995-2018
The Biomarkers of Exposure vs Effect: Improving the Scientific Basis for Risk Assessment Project, led by James Swenberg, Ph.D., continues to deliver cutting-edge discoveries. Utilizing stable-isotope labeled formaldehyde in animal exposure studies, recent data has shown that ultra-low levels of inhaled formaldehyde do not cause the formation of exogenous (labeled) DNA damage products in any of the tissues examined. Conversely, unlabeled formaldehyde, meaning formaldehyde formed endogenously, led to formaldehyde-induced mono-adducts and formaldehyde-induced DNA Protein Crosslinks (DPCs) in all of the tissues examined. These data indicate that formaldehyde is produced intracellularly and is unaffected by ultra-low doses of exogenous exposure. Swenberg's lab continues to keep up with developing technology and instrumentation. They recently developed a novel and accurate method to detect formaldehyde-DPCs using an advanced Orbitrap mass spectrometer. The researchers have used this method to study the formation of endogenous formaldehyde-DPCs, as they may be an important source of DNA damage. For instance, in one of their many collaborations, they are analyzing the endogenous formaldehyde DNA damage products in bone marrow of patients with Fanconi anemia. Additionally, in parallel with their recent discoveries of formaldehyde-DNA mono-adducts and formaldehyde-DPCs in rats exposed to 2-ppm formaldehyde for 28 days, exogenous N6-formyllysine adducts were found only at the point of initial contact. Lastly, Swenberg and his researchers have been finalizing three important publications detailing the hepatic DNA oxidation products formed from chronic exposure to PCBs, PeCDF and TCDD. This research, which was done in collaboration with the National Toxicology Program, will lead to a better understanding of the hepatic toxicity and carcinogenesis associated with PCB exposure.