Arsenic is one of the world’s most ubiquitous environmental toxicants, with humans being exposed from air, food and water. However, elevated arsenic levels in drinking water are the major cause of toxicity, and are a health issue in many of the communities in this country that are in proximity to Superfund sites.
This Research Project led by Dr. Paul Russell, will use functional toxicogenomics and proteomics technologies to uncover the genes and pathways that determine cellular responses and genetic susceptibilities to arsenic, cadmium, chromium, nickel and other heavy metals that contaminate Superfund sites.
Carbon tetrachloride (CCl4) is a Superfund toxicant (CERCLA Priority #47) that usually escapes into the environment as a gas, or it is sometimes found in water and soil. The liver is a primary target of the toxicity of CCl4. Exposure to high levels of CCl4 induces liver damage, inflammation and fibrosis. In healthy people, CCl4-induced liver injury and fibrosis can reverse when the exposure is discontinued.
Dr. Michael Karin's project studies how Superfund toxicants and mixtures thereof increase liver cancer risk. Our efforts will focus on specific progenitor cells responsible for generation of hepatocellular carcinoma (HCC), the most common form of liver cancer, in mice administered diethylnitrosamine (DEN), an hepatocarcinogen that represents the nitrosamine class of Superfund substances.
Superfund site xenobiotics and other environmental toxicants are human health hazards whose toxicity is, in part, associated with altered patterns of gene expression. The goal of this project is to provide molecular mechanisms and models for exposure, focusing on the “classic” xenobiotic receptors (XenRs) PXR and CAR, and their induction of gene networks encoding the Phase I, II and III clearance pathways.
Fluorescent reagents based on conjugate polymers have proven useful for inexpensive and field-portable detection of nanogram to femtogram levels of nitroaromatic explosives, which have been commercialized. Conjugated polymers are advantageous in such sensing applications, because delocalization of their excited state exciton along the polymer chain provides sensor amplification and remarkable sensitivity. This technology will be adapted to design tests for separating and detecting toxicants, such as polycyclic aromatic hydrocarbons, found at Superfund sites.
Soils and waters with high levels of toxic heavy metal(loid)s such as arsenic, cadmium and mercury are detrimental to human and environmental health. These three metal(loid)s are among the Superfund's top 7 priority hazardous substances.
UCSD Superfund Research Center
University of California, San Diego
9500 Gilman Drive, Mail Code 0722
La Jolla, CA 92093-0722