Environmental Factor, November 2011, National Institute of Environmental Health Sciences
Grollman takes top award at EMS meeting
By Eddy Ball
Grollman is director of the Laboratory of Chemical Biology(http://www.lcb.stonybrook.edu/) at Stony Brook University. He is a member of NIEHS' Environmental Health Sciences Review Committee and a former member of the Board of Scientific Counselors. (Photo courtesy of Arthur Grollman and Stony Brook University)
NIEHS grantee Arthur Grollman, M.D., received this year's EMS Award Oct. 18 at the Environmental Mutagen Society (EMS) 42nd Annual Meeting(http://www.ems-us.org/AM2011/overview.asp) in Montreal. As part of his honor, Grollman presented a lecture on “Human Exposure: Unraveling the Mystery of a Global Environmental Disease,” reporting on the latest developments in his quest to understand aristolochic acid-induced kidney damage and upper urothelial cancers (UUC).
Grollman(http://www.lcb.stonybrook.edu/node/116) is Distinguished Professor of Pharmacological Sciences, Evelyn G. Glick Professor of Experimental Medicine, and director of the Zickler Laboratory of Chemical Biology at the State University of New York at Stony Brook. As a result of research by him and his colleagues in the U.S. and Europe, Grollman said in a 2010 interview, “Aristolochic acid ... now joins aflatoxin and vinyl chloride as established human chemical carcinogens with distinct TP53 mutational signatures.”
With his award, Grollman joins a distinguished list of scientists honored with the EMS Award(http://www.ems-us.org/Content/About/pastemsaward.asp) since 1972, in recognition of outstanding research contributions in the area of environmental mutagenesis. The list includes NIEHS lead researcher Samuel Wilson, M.D., last year (see story(http://www.niehs.nih.gov/news/newsletter/2010/december/science-environmental.cfm)), grantee Leona Samson, Ph.D., in 2001, and lead researcher Thomas Kunkel, Ph.D., in 1997.
Endemic nephropathy in the Balkans
The author of more than 200 peer-reviewed papers, Grollman began his research on the herb Aristolochia, and its link to kidney failure and urothelial cancer in 2005, with an epidemiological study of people with endemic nephropathy in Croatia, one of several areas in the Danube river basin where chronic renal disease is endemic.
Further investigations provided more evidence that exposure to Aristolochia, as a consequence of consuming contaminated wheat grain from cultivated fields where Aristolochia grows wild, is strongly associated with increased risk of developing the disease. Because this herb, which grows worldwide, is also used by millions of people as a medicine, diseases linked to it constitute a major global public health problem.
Since his initial publication on Aristolochia, Grollman has given many talks on the subject, including one last year (see story(http://www.niehs.nih.gov/news/newsletter/2010/may/science-herbal.cfm)), and published eight additional papers on aristolochic acid-induced disease. Grollman extended his epidemiological findings to include metabolic and genetic studies. His latest research, currently in press for the journal Kidney International, describes a robust biomarker of exposure to aristolochic acid and a specific biomarker characteristic of aristolochic acid-induced UUC. Its findings were the basis of his EMS Award lecture.
Studies of human tissues
Grollman and his team of researchers extracted DNA from renal cortex and tumor tissue of 67 residents, from regions known to harbor endemic nephropathy, who had undergone nephroureterectomy for UUC. They then compared their findings with results from a cohort of 10 individuals with UUC from nonendemic areas, who served as controls.
The team tested for the presence of aristolactam (AL)-DNA adducts, which concentrate in the renal cortex. AL-DNA adducts are formed by the reaction of aristolochic acid with genomic DNA. They also tested for unique mutations in TP53, a tumor-suppressor gene, which Grollman and colleagues established as a biomarker for aristolochic acid nephropathy with a study published in September (see story(http://www.niehs.nih.gov/news/newsletter/2011/november/science-extramural/#two)).
They found that AL-DNA adducts were present in 70 percent of endemic cases of UUC patients, and in 94 percent of patients who carried these specific mutations in TP53, neither of which were detected in patients with UUC residing outside of this region. Their results provide molecular epidemiologic evidence that in genetically susceptible individuals, dietary exposure to aristolochic acid is causally related to endemic nephropathy and UUC.