Environmental and Molecular Mutagenesis (EMM) Editor's Choice - March 2013
The Editor's Choice for March is "Evaluation of Gene Expression Changes in Human Primary Uroepithelial Cells following 24-Hr Exposures to Inorganic Arsenic and Its Methylated Metabolites," by Janice W. Yager, R. Robinan Gentry, Russell S. Thomas, Linda Pluta, Alina Efremenko, Michael Black, Lora L. Arnold, James M. McKim, Paul Wilga, Gary Gill, Key-Young Choe, and Harvey J. Clewell.
Dr. Yager and colleagues have been studying mechanisms and markers of arsenic carcinogenesis for many years. Arsenic exposures in the parts per billion ranges may result in cancer years later. Arsenic is found naturally in water, air, plants and animals. Unexpected high levels of arsenic were recently reported for rice. Arsenic is not a direct-acting mutagen, and its dose response is highly non-linear. While arsenic has been known to be a human carcinogen for many years, there are still questions as to mechanisms of action. Understanding mechanisms for arsenic carcinogenicity are difficult in part because standard animal cancer bioassays do not directly mimic what occurs following human exposures to arsenic. The present work reports on specific changes in gene expression when human uroepithelial cells were exposed to mixtures of inorganic arsenic and its metabolites. The authors report specific cell signaling pathway perturbations that might be associated with the carcinogenic action of arsenic. This study is the first to identify no effect levels for arsenical induced cell signaling perturbations, which are consistent with the proposed threshold for arsenic-induced cancers. The report also identified both quantitative and qualitative variability between individuals in response. These data strengthen the concept of a potential threshold or a concentration demonstrating a dose-dependent transition in response and provide additional support for an alternative approach to arsenic cancer risk assessment that is in contrast to the standard method. Environ. Mol. Mutagen., 54:2 (82-98) © 2013 Wiley Periodicals, Inc.