Superfund Research Program
Genetic and Epigenetic Mechanisms of Toxicities of Mixtures of Aromatic Hydrocarbon and Metal Contaminants to Aquatic Populations (ARRA Funded)
Project Leader: Isaac I. Wirgin
Grant Number: P42ES010344
Funding Period: 2009-2011
Project Summary (2009-2011)
Urban and industrial Superfund sites usually contain complex mixtures of contaminants, including aromatic hydrocarbons and heavy metals. The Hudson River Estuary has individual Superfund sites for PCBs, PCDD/Fs and chromium (Cr), along with some of the highest sediment levels of PAHs of any estuary in the U.S. After decades of debate, the Hudson River PCBs Superfund site is designated for remediation beginning in the spring of 2009. In the late 1970s, Atlantic tomcod from the Hudson River exhibited one of the highest prevalences of tumors (hepatocellular carcinomas) ever observed in a natural population along with a dramatically truncated age structure. In a combination of field and laboratory studies, Dr. Wirgin’s research group is determining the prevalence of hepatocellular carcinomas and the age structure of the Hudson River tomcod population over the course of site remediation. The mechanistic basis of hepatic neoplasia and other toxicities in the population will also be studied. In controlled laboratory studies, Dr. Wirgin is determining the sensitivity of young life-stages of tomcod to a suite of epigenetic alterations (DNA methylation and histone modifications) at global and gene-specific levels resulting from exposures to Cr, benzo[a]pyrene, and their mixtures. He will also compare the sensitivities of different individuals and populations of tomcod to sensitive epigenetic changes. In parallel studies, the prevalence of these epigenetic changes are compared in tomcod from known contaminated sites in the Hudson River and from cleaner estuaries. Because the etiology of chemical toxicities, including hepatic neoplasia, probably involve a combination of genetic damage and altered gene expression, the researchers will also explore the effect of co-exposure to Cr (VI) on the sensitivity of tomcod to the generation of DNA adducts at the K-ras oncogene from B[a]P exposure. Our studies will complement those from other investigators in this program by evaluating the taxa conservation of mechanisms of epigenetic and genetic toxicity and the applicability of their results to real-world in vivo environmental exposures of natural populations at Superfund sites.