Superfund Research Program
Site Assessment, Cleanup, Analysis and Bioremediation
Project Leader: Kirby C. Donnelly
Grant Number: P42ES004917
Funding Period: 1995 - 2000
- Project Summary
Final Progress Reports
Studies conducted during the previous year have focused on two major issues relevant to site assessment. These include bioavailability and complex mixture interactions. An in vivo study was conducted to measure the bioavailability of PAHs in a coal tar amended soil. Rodents administered a coal tar amended feed expressed a significant increase in DNA adduct levels in both the liver and the lungs when compared to rodents fed soil amended with coal tar. A small, but non-significant increase in excretion of 1-OH-pyrene was observed in rodents fed freshly spiked soil when compared to those fed an aged soil. DNA adduct formation was measured in rodents administered a binary mixture of benzo(a)pyrene (BAP) and pentachlorophenol (PCP). PCP exhibited an antagonistic effect on formation of BAP adducts to DNA in infant mice, while BAP adducts were increased in hepatic and lung DNA of adult mice exposed to the binary mixture. The results suggest that PCP alters the metabolism of BAP in both infant and adult mice through different mechanisms, and that infants were not susceptible to the potentiative effects of PCP observed in adult mice. To investigate this effect further, trp53+/+ (WT) and trp53-/- (KO) mice were exposed to BAP alone and in combination with PCP. In wild type mice (WT), PCP inhibited total DNA adduct levels in hepatic DNA, but had no effect on lung adduct levels. In KO mice, PCP had no effect on adduct levels in either the lungs or liver. The results suggest that the antagonistic effects of PCP on BAP adduct formation in WT mice may be due to the induction of p53 protein and its response pathways, and/or inhibition of important enzymes in the conversion of BAP to a diol epoxide.