Superfund Research Program
Epigenetic Effects on Individual Susceptibility to Heavy Metal and Polycyclic Aromatic Hydrocarbon- Induced DNA Damage
Project Leader: Moon-shong Tang
Grant Number: P42ES010344
Funding Period: 2000 - 2006
Project Summary (2000-2006)
The goal of this project is to investigate the carcinogenicity of heavy metals such as arsenic, nickel and chromium, and polycyclic aromatic hydrocarbons (PAHs) such as benzo(a)pyrene. Researchers hypothesize that the carcinogenicity of nickel, arsenic and chromium may be partly due to their ability to induce DNA hypermethylation, which in turn enhances the susceptibility of methylated tumor suppressor genes and protooncogenes to bulky carcinogen-induced DNA damage and mutations. Further, project investigators hypothesize that targeted DNA damage, rather than selection, is the major determinant of the p53 mutation spectrum in human cancer, and that the CpG methylation status of an individual p53 gene may determine the susceptibility of this gene to DNA damage and mutation. Researchers are determining the ability of nickel, arsenic, and chromium to induce changes in the methylation status of the p53 gene and, consequently, in the susceptibility of this gene to BPDE induced-DNA damage. Additionally, the effect of nickel, arsenic and chromium treatment on the repair of BPDE-DNA adducts in the p53, B-actin and HPRT gene is being investigated. This research is improving understanding of the mechanisms of metal-induced and PAH-induced carcinogenesis.