A senior biophysicist at the U.S. Department of Energy’s Brookhaven NationalLaboratory (BNL) has been named the recipient of the 2002 Environmental MutagenSociety (EMS) Award.
Dr. Richard Setlow is being recognized for his research contributions to thefield of environmental mutagenesis, which involves the study of how variousagents in the environment, such as chemicals and radiation, lead to DNA damageand how that damage is repaired.
The award will be formally announced at the annual EMS meeting in Anchorage,Alaska, on April 30. Setlow will receive a plaque and monetary award.
‘I am pleased to be chosen for this award,’ Setlow said. ‘Iam gratified that discoveries I’ve made have had wide application in many fieldsand have advanced scientific understanding of how genetics, the environment,and human health are interconnected.’
Specifically, Setlow is being honored for his discovery of nucleotide excisionrepair and the development of a method called bromouracil photolysis to studyexcision repair. He was also cited for his discovery of a crucial link betweenunrepaired DNA damage and cancer.
Almost forty years ago, Setlow and his colleagues at Oak Ridge National Laboratorydiscovered that certain DNA defects caused by ultraviolet light lead to biologicaldamage.
He also showed that, in normal bacterial cells, these defects could be removedby cellular enzymes, a process known as nucleotide excision repair. This repaircuts out the damaged regions and patches the resulting holes.
The groundbreaking research led to great interest in repair, since certaingenetic diseases stem from inherited deficiencies in DNA repair.
In the early 1970s, Setlow and James Regan, a colleague at Oak Ridge NationalLaboratory, developed bromouracil photolysis, a method to measure DNA repairthat became a standard technique. They incorporated bromouracil, an analog ofthymine, into repaired patches of DNA.
Exposure of the repair patches to long-wavelength ultraviolet light resultedin DNA breaks in the bromouracil. They were able to calculate the numbers andsizes of the repaired regions arising from chemical or physical agents in theenvironment from the ultraviolet dose and numbers of breaks.
At BNL in the early 1990s, Setlow and his colleagues began investigating therole of melanoma-susceptibility genes and tumor-suppressor genes in causingmelanomas. They found that the most serious form of skin cancer, known as malignantmelanoma, is induced by all wavelengths of the sun’s ultraviolet rays.
Based on experiments using tropical fish, which, like humans, develop melanomafrom exposure to sunlight, this surprising discovery contradicted the long-heldbelief that only short ultraviolet light wavelengths were potentially harmful.
Currently, Setlow is working with Japanese collaborators on NASA-funded researchto estimate the magnitude of mutations in sperm of astronauts resulting fromexposure to high-energy cosmic rays in outer space. As a model, they are usingfish native to Japan, called medaka.
Male fish are exposed to energetic nuclei from BNL’s particle accelerator,the Alternating Gradient Synchrotron, and mated with unexposed females. Mutationsin the sperm result in color changes in fertilized embryos that are easily observedbecause the embryos are transparent.
Among his many honors, Setlow won the 1988 Enrico Fermi Award, the most prestigiousscientific award given by the U.S. Department of Energy, for his contributionsto the fields of radiation biophysics and molecular biology.
