Environmental and Molecular Toxicology
People and animals are exposed to a complex mixture of toxins and carcinogens throughout their lifetimes, sometimes resulting in disease and genetic mutation. Though a source of vital nutrients, even the food we eat is sometimes a vehicle for toxins and carcinogens. From tackling the causes of cancer to cleaning hazardous waste with live organisms, Utah State University scientists are creating innovative solutions to real-world problems in health and the environment.
Why this research is important
Which of the thousands of chemicals we are exposed to daily are really dangerous, and how much exposure causes harm? How do these chemicals affect our environment? Are they cancer-causing? Do they cause birth defects, nervous system damage, cardiovascular or lung disease? In answering these questions, USU toxicology researchers are building scientific knowledge that is used to shape national standards that improve our health and environment. Toxicology research leads to societal decisions that can ensure lead-free playgrounds, safer drinking water, cancer reduction, and elimination of toxic waste sites.
Our toxicologists are developing ways to degrade environmental pollutants, and were among the first to use a naturally-occurring fungus to ?digest? and detoxify chemical waste. USU food scientists are identifying the chemicals naturally found in our diets that contribute to cancer and those that aid in its prevention—an emerging dietary treatment approach that reduces the impact of carcinogens naturally found in food. However, despite many scientific advances, there are many problems that remain to be tackled.
What is toxicology?
Toxicology is the scientific understanding of the harmful effects of natural and synthetic chemicals at all levels—whether large-scale environmental pollutants or small-scale carcinogens that have an incremental effect over time. At Utah State University, researchers from multiple disciplines are using this understanding to ensure the safety of our food, water, and the environment.
Scientific Perspective
USU researchers are discovering the molecular mechanisms of disease caused by natural and synthetic chemicals. The unifying goal of these efforts is to improve the health of people, animals and our environment, while developing solutions to real-world problems. Our research tools include a spectrum of techniques ranging from cell culture to whole animal capabilities. At USU, we maximize molecular approaches using genomics to understand chemical reactions in living organisms.
Topical Overview
Mechanisms of Cancer
According to the National Cancer Institute, diet and lifestyle are responsible for approximately one-third of cancer incidence. Our food contains thousands of naturally-occurring carcinogens, such as aflatoxin and heterocyclic amines. USU investigators are determining how these chemicals cause cancer at the gene level, such as how they mutate p53 tumor suppressor genes and affect apoptosis. Because most carcinogens require modification by cytochrome P- 450s (CYPs) as well, the role of these enzymes in cancer risk and resistance is also being explored. Human lung cells transformed with various CYP isoforms are being used as models to dissect molecular events in lung carcinogenesis, including changes in cellular signal transduction and gene expression. Microarray expression analysis and realtime PCR are among the tools used to identify gene clusters affected by these carcinogens. New molecular diagnostic tools are being developed to determine the risk posed to human health by dietary and environmental carcinogens.
Chemoprevention
Studies show that many natural and synthetic compounds (like some antioxidants and plant micronutrients) can actually prevent cancer in animals, and may very likely have the same beneficial effect in people. USU researchers are determining how these ?chemopreventives? increase expression of protective enzymes, such as glutathione S-transferase, or reduce the extent to which carcinogens are enzymatically activated by CYPs. Some of this work is being conducted using cloned gene products. A longrange goal of this research is the eventual development of ?cancer-fighting? diets.
Mechanistic Toxicology
USU researchers are using genomics-based and molecular biology techniques to study mechanisms of disease caused by toxic agents at the molecular and genetic levels. Events being investigated include induction of DNA mutations that contribute to cancer and other diseases, and the mechanisms of cellular responses to such damage, including DNA repair, gene expression, and cell cycle control. Among the numerous toxic agents under study are asbestos, polycyclic aromatic hydrocarbons, aflatoxins, iron, pyrrolizidine alkaloids, and urban particulate matter (PM2.5 and PM10).
Role of Free Radicals in Disease
USU is a recognized leader in basic research of free radical chemistry, especially ironbinding and transport proteins (such as ferritin), the role of iron and free radicals in cancer and cardiovascular disease, as well as the body?s defense mechanisms against free radicals. Proteins involved in iron transport and metabolism in humans are being investigated by sequential addition of genes encoding these proteins into E. coli grown on increasing amounts of iron. Site-directed mutagenesis aids researchers in sorting out the molecular determinants of functional metal binding and catalysis. These and related studies are revealing the mechanisms involved in iron transport, iron metabolism, and iron-induced cellular damage.
Bioremediation Using Microbes and Plants
USU researchers pioneered the use of the white rot fungus Phanerochaete chrysosporium to degrade persistent toxic pollutants such as PCBs, dioxin, DDT and TNT. Several laboratories on campus are now investigating the use of microbes isolated from the environment (such as mycobacteria) and plants to sequester toxic heavy metals such as arsenic, cadmium, lead, and mercury. These innovative bioremediation technologies have been successful in removing various pollutants in actual field settings like abandoned mines and hazardous waste dumps. Degradation of chemicals by Phanerochaete chrysosporium involves peroxidases and several other enzymes. The peroxidases use hydrogen peroxide to generate powerful oxidants that can degrade otherwise recalcitrant chemicals. These enzymes are rather non-specific, and the fungus has other activities to support the degradation of a wide variety of chemicals, including synthetic polymers. Current research is directed toward engineering better enzymes and better fungi to more rapidly degrade a wider variety of chemicals.