Superfund Research Program

Genotoxicity of Complex Mixtures

Project Leader: Kirby C. Donnelly
Grant Number: P42ES004917
Funding Period: 2000-2008

Project-Specific Links

Final Progress Reports

Year:   2007  2004 

Studies have been initiated in this project to validate measurements of DNA adducts as a biomarker of carcinogenicity.   Wood preserving waste was collected from a contaminated site in the United States.  The collected mixture was initially extracted into acid, base and neutral fractions to isolate chlorophenols from polycyclic aromatic hydrocarbons (PAHs).  Two aliquots of the neutral fraction were further fractionated to produce a PAH-enriched isolate and a dioxin (PCDD)-enriched isolate.   These fractions were then tested in a battery of short-term in vitro and in vivo bioassays.  The autoradiograms (below), along with the CPM values of the radioisotope ³²P, suggest that the DNA adducts formed using a reconstituted mixture, made of the seven USEPA carcinogenic PAHs plus pentachlorophenol, did not produce the same intensity of DNA adduct frequency as were observed using the PAH fraction.  These data have important implications for risk assessment in that they suggest that chemicals, or chemical interactions, exist that increase the genotoxicity of complex PAH mixtures.  A 40-week tumor study using an infant male mouse model was initiated in July 2004 using selected fractions to confirm results of the short-term bioassays.