The goals of the UC Berkeley Superfund program are to improve understanding of the relationship between exposure and disease, provide better human and ecological risk assessments, and develop a range of prevention and remediation strategies to improve and protect public health, ecosystems and the environment. The program’s themes are to: a) apply functional genomics, proteomics, transcriptomics, and nanotechnology to better detect arsenic, mercury, benzene, polycyclic aromatic hydrocarbons, trichloroethylene, and other Superfund priority chemicals in the environment; b) to evaluate their effects on human health, especially the health of susceptible populations such as children; c) remediate their presence; and d) reduce their toxicity.
UC Berkeley’s program builds on the strengths of UC Berkeley and Lawrence Berkeley National Laboratory in engineering, chemistry, and molecular epidemiology. The program consists of six interrelated projects (three with a biomedical research focus and three with a non-biomedical research focus) and five cores.
The major objectives are to:
- Develop and apply novel biomarkers and exposure assessment tools in epidemiology studies [Project 1] [Project 3] [Project 5]
- Enhance our knowledge of the toxic effects of arsenic, especially in early life [Project 3]
- Determine the role of environmental exposure to benzene and polycyclic aromatic hydrocarbons in the development of childhood leukemia [Project 1]
- Identify genes that confer susceptibility to chemical toxicity through the application of functional genomics [Project 2]
- Expand our ability to remediate toxic waste sites at a lower cost using nanotechnology and bioremediation [Project 4] [Project 6]
- Improve our ability to measure chemical species in the environment using nanotechnology [Project 4] [Project 5]
- Promote the exchange of information among scientists, regulators, and other interested parties in order to translate basic research finding into appropriate policies and public health interventions [Core B]
- Move our research findings into application through technology transfer [Core B]
- Provide training that is interdisciplinary and imparts skills in the translation of scientific results to a new generation of scientists in the many disciplines relevant to the Program [Core E]
2006-2011 Program Summary
The University of California-Berkeley Superfund Basic Research Program began in 1987. The goal is “to improve understanding of the relationship between exposure and disease; provide better human and ecological risk assessments; lower cleanup costs; and develop a range of prevention strategies to improve and protect public health, ecosystems and the environment.” The Program builds on the strengths of UC Berkeley and Lawrence Berkeley National Laboratory in engineering, chemistry and molecular epidemiology, and consists of six interrelated basic and applied research projects. The overall theme of the program is “The application of functional genomics, proteomics, transcriptomics, and nanotechnology to better detect arsenic, mercury, benzene, polycyclic aromatic hydrocarbons, trichloroethylene and other Superfund priority chemicals in the environment; evaluate their effects on human health, especially the health of susceptible populations such as children; and remediate their presence and reduce their toxicity. Themes of the individual projects include using proteomics and transcriptomics to study the role of chemical exposure in causing childhood leukemia; taking a functional genomic approach to finding susceptibility genes; applying novel biomarkers to study the health effects of arsenic; improving bioremediation of toxic chemicals through the application of -omic technologies and nanotechnology, and developing nano-scale sensors of chemical species in the environment. A toxicogenomics laboratory core and a computational biology core will assist researchers in creating tools for use in epidemiological and risk research. The new research translation core will facilitate intensive discussions between investigators and government audiences, and generate new initiatives to increase understanding of the significance and applicability of emerging areas of research to public health protection through policy, interventions, and individual actions. The training core will prepare graduate and post-doctoral students to conduct multidisciplinary research into the effects of environmental factors on health, and to develop technological solutions to prevent or mitigate the harm resulting from Superfund priority chemicals.
2010 Program Highlights
Project 2: Functional profiling of susceptibility genes
Leaders: Christopher Vulpe and Luoping Zhang
The most important thing Project 2 investigators have discovered in the past year is that a protein called N6AMT1 (short for ‘N-6 adenine-specific DNA methyltransferase 1’) can metabolize arsenic compounds and lower their toxicity. This is a novel finding and a paper on this is in press in Environmental Health Perspectives. The investigators first used yeast to discover that mutated yeast lacking the gene MTQ2 were altered in their response to arsenic exposure. The human equivalent of yeast MTQ2 is N-6 adenine-specific DNA methyltransferase 1 (N6AMT1). Enhanced expression of N6AMT1 in human bladder cells significantly increased their resistance to the toxicity of arsenic and its metabolites and N6AMT1 was shown to methylate arsenic to a non-toxic metabolite. The investigators showed that N6AMT1 was able to convert monomethylarsonous acid (MMAIII), the most toxic arsenic species, to the less toxic dimethylarsonic acid (DMA) when over-expressed in human bladder cells. The enhanced expression of N6AMT1 in these cells decreased cytotoxicity of both iAsIII and MMAIII. Moreover, N6AMT1 is expressed in many human tissues at variable levels, although lower than those of AS3MT, supporting a potential participation in arsenic metabolism in vivo. Since MMAIII is the most toxic arsenical, our data suggest that N6AMT1 has a significant role in determining susceptibility to arsenic toxicity and carcinogenicity due to its specific activity in methylating MMAIII to DMA, and other unknown mechanisms.
Project 3: Arsenic biomarker epidemiology
Leaders: Patricia Buffler and Martyn Smith
Arsenic in drinking water causes increased mortality from several cancers, ischemic heart disease, bronchiectasis, and other diseases. Project 3 investigators discovered this year that death from tuberculosis is also more likely to occur following arsenic exposure. Their paper, to be published in the American Journal of Epidemiology, presents the first evidence relating arsenic exposure to pulmonary tuberculosis, by estimating mortality rate ratios for Region II of Chile compared to Region V for the years 1958-2000. The authors compared mortality rate ratios with time patterns of arsenic exposure, which increased abruptly in 1958 in Region II and then declined starting in 1971. Tuberculosis mortality rate ratios in men started increasing in 1968, ten years after high arsenic exposure commenced. The peak male five-year mortality rate ratio occurred during 1982-86 (RR=2.1, 95% CI 1.7-2.6, P<0.001), and subsequently declined. Mortality rates in women were also elevated, but with fewer excess pulmonary tuberculosis deaths (359 among men and 95 among women). The clear rise and fall of tuberculosis mortality rate ratios in men following high arsenic exposure is consistent with a causal relationship. The findings are biologically plausible in view of evidence that arsenic is an immunosuppressant and also a cause of chronic lung disease. Finding weaker associations in women is unsurprising, since this is true of most arsenic-caused health effects. Confirmatory evidence is needed from other arsenic-exposed populations and studies are on-going in other populations.