| Intracellular Calcium Disturbances Induced by Arsenic and Its Methylated Derivatives in Relation to Genomic Damage and Apoptosis Induction Ana-Maria Florea,1,2 Ebenezer N. Yamoah,2 and Elke Dopp1 1Institute of Hygiene and Occupational Medicine, University Hospital, Essen, Germany; 2Department of Otolaryngology, Center for Neuroscience, University of California, Davis, California, USA Abstract
Arsenic and its methylated derivatives are contaminants of air, water, and food and are known as toxicants and carcinogens. Arsenic compounds are also being used as cancer chemotherapeutic agents. In humans, inorganic arsenic is metabolically methylated to mono-, di-, and trimethylated forms. Recent findings suggest that the methylation reactions represent a toxification rather than a detoxification pathway. In recent years, the correlation between arsenic exposure, cytotoxicity and genotoxicity, mutagenicity, and tumor promotion has been established, as well as the association of arsenic exposure with perturbation of physiologic processes, generation of reactive oxygen species, DNA damage, and apoptosis induction. Trivalent forms of arsenic have been found to induce apoptosis in several cellular systems with involvement of membrane-bound cell death receptors, activation of caspases, release of calcium stores, and changes of the intracellular glutathione level. It is well known that calcium ion deregulation plays a critical role in apoptotic cell death. A calcium increase in the nuclei might lead to toxic effects in the cell. In this review, we highlight the relationship between induced disturbances of calcium homeostasis, genomic damage, and apoptotic cell death caused by arsenic and its organic derivatives. Key words: apoptosis, arsenic, genomic damage, intracellular calcium. Environ Health Perspect 113:659-664 (2005) . doi:10.1289/ehp.7634 available via http://dx.doi.org/ [Online 10 February 2005]
Address correspondence to E. Dopp, University of Duisburg-Essen, University Hospital Essen, Institute of Hygiene and Occupational Medicine, Hufelandstraße 55, 45122 Essen, Germany. Telephone: 0201-723-4578. Fax: 0201-723-4546. E-mail: elke.dopp@uni-essen.de The authors declare they have no competing financial interests. Received 4 October 2004 ; accepted 9 February 2005.
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