Media Contact: Dave Lavallee 401-874-2116
URI scientist awarded $1.1 million federal
grant to study cells exposed to carcinogens
Goal is to determine how cell mutations lead to cancer
KINGSTON, R.I. -- September 2, 2003 -- What happens to cells after they are exposed to substances like cigarette smoke, diesel fumes, or charred meat? University of Rhode Island biomedical scientist Bongsup Cho is hoping to answer that question. The answer could solve the puzzle of how precisely cancer begins.
Hell have help in his quest with a four-year, $1.1 million National Institutes of Health grant to examine how DNA is altered when the body is exposed to toxins. "Researchers are now finding that the environment is much more important than genetics and thats why we want to look at cancer in the initiation stage," Cho said. The grant is a major boost for Cho, who, for many years has been focusing on the structural aspect of DNA mutation following exposure to carcinogens. In the past he has been awarded about $270,000 in grants from the American Cancer Society, which laid the foundation for this more ambitious NIH project.
The Kingston resident received notification of the award just days before he and his colleagues at the URI College of Pharmacy opened a new $2 million core laboratory that is being used by seven colleges in the state to enhance biomedical research. The lab is part of a $7.6 million NIH grant awarded to URI that has led to the establishment of the Rhode Island Biomedical Research Infrastructure Network. Cho is a co-director of the lab.
"I think the NIH believed that I have a novel approach for solving problems in basic cancer research," Cho said. "Cancer is a disease that often takes years to develop through various stages. When a tumor develops or metastasis begins, the cancer is already in the later stages. I am interested in the initiation stage." Cho said structural mapping of DNA adducts is crucial to understanding the initiation of carcinogenesis and ultimately in designing preventative strategies and medications to combat the disease. "My hypothesis is that carcinogens become toxic when they are metabolized. These reactive metabolites bind to DNA and create adducts, otherwise known as mutated versions of DNA," Cho said. "When a DNA adduct is formed, the structure of the natural DNA base is altered, causing multiple mutations. A damaged DNA base can exist in several different structural forms, making it very difficult to pinpoint which structures are responsible for which mutations and why. Therefore, it is important to establish a clear linkage between the shape of damaged DNA and the observed mutations."
This grant will help Cho to unravel some of the mysteries. One of his experiments may provide a systematic basis for investigating mutagenesis in a simulated biological environment for the first time. "The research will introduce fluorine nuclear magnetic resonance spectroscopy as a powerful structural biology tool in investigating the mechanisms of arylamine mutagenesis," he said. "The approach is a typical example of chemical biology and will help us mimic what happens in the body," Cho said. "Through this work, we hope to understand at the molecular-genetic level how the cell repair system works or doesnt work when carcinogens are bound to DNA," Cho said.
The URI scientist stressed that this kind of basic research is crucial also for drug development. A case in point, he said, is a recent highly publicized clinical test of a topical lotion that helps repair DNA damage in skin cancer. The lotion containing a repair enzyme effectively removes the DNA adducts induced by ultraviolet light, and replaces it with newly made, undamaged DNA."
For Further Information: Bongsup Cho 401-874-5024