University at Buffalo faculty member Dr. Xuefeng Ren, assistant professor of epidemiology and environmental health in the School of Public Health and Health Professions, has received a $1.4 million grant from the National Institutes of Health to investigate the mechanisms of arsenic carcinogenesis — the process by which exposure to arsenic transforms normal cells into cancer cells.
Chronic exposure to arsenic, an element widely distributed in the natural environment, affects up to 100 million people in 70 countries, including the United States. It can lead to increased morbidity and mortality from both non-cancerous and cancerous effects, including diabetes, peripheral neuropathy, cardiovascular diseases, and cancers of the bladder, lung, kidney, and skin.
Many environmental scientists are wrestling with ways to deal with the problem at its most ubiquitous source: groundwater that is naturally contaminated with inorganic arsenic compounds. Dr. Ren and his team, however, will employ an integrated approach that combines cell and molecular biology with epidemiology in order to decipher how chronic arsenic exposure works in the body. This could lead to new methods of prevention and treatment.
Dr. Ren says that although the relationship between arsenic exposure and cancer is well documented, the mechanisms by which arsenic participates in the production of tumors are not clear. He says researchers theorize that arsenic causes changes in the epigenome, which is the record of chemical changes to the DNA and histone proteins that affect both gene expression and carcinogenesis.
“This study will examine the molecular mechanisms of MMA (III) or monomethylarsenous acid, a substance composed of highly toxic arsenic metabolites, in inducing or precipitating the malignant transformation of human cells,” he says.
He explains that chromatin is the mass of genetic material in the nucleus of a cell composed of DNA and proteins that condense to form chromosomes. “A unique aspect of this study is that it is expected to identify the early and likely driving chromatin/epigenetic changes responsible for aberrant gene expression in MMA (III)-induced cell malignant transformation,” Dr. Ren says.
His long term goal is to define the effects and consequences of chronic arsenic exposure on the epigenome, which could allow targeted therapeutic interventions with epigenetic-targeting drugs. “Moreover,” he says, “by identifying the locations of arsenic-induced chromatin alterations, we hope to provide a completely new type of epigenetic biomarker for arsenic-associated cancers. This will allow us to identify people at high risk for developing these cancers.”
UB co-investigators with Dr. Ren on the study are Dr. Michael Buck, assistant professor, department of biochemistry, School of Medicine and Biomedical Sciences, and director of the UB Stem Cell Sequencing/Epigenomics Center (WNYSTEM), and Dr. Daniel Gaile, assistant professor, department of biostatistics, School of Public Health and Health Professions. Other significant contributors include Dr. Xiaojuan Guo and Dr. Hongmei Wu of Wenzhou Medical University, China, and Dr. Allan H. Smith of the University of California, Berkeley.