title: Cellular arsenic transport pathways in mammals.
abstract: Natural contamination of drinking water with arsenic results in the exposure of millions of people world-wide to unacceptable levels of this metalloid. This is a serious global health problem because arsenic is a Group 1 (proven) human carcinogen and chronic exposure is known to cause skin, lung, and bladder tumors. Furthermore, arsenic exposure can result in a myriad of other adverse health effects including diseases of the cardiovascular, respiratory, neurological, reproductive, and endocrine systems. In addition to chronic environmental exposure to arsenic, arsenic trioxide is approved for the clinical treatment of acute promyelocytic leukemia, and is in clinical trials for other hematological malignancies as well as solid tumors. Considerable inter-individual variability in susceptibility to arsenic-induced disease and toxicity exists, and the reasons for such differences are incompletely understood. Transport pathways that influence the cellular uptake and export of arsenic contribute to regulating its cellular, tissue, and ultimately body levels. In the current review, membrane proteins (including phosphate transporters, aquaglyceroporin channels, solute carrier proteins, and ATP-binding cassette transporters) shown experimentally to contribute to the passage of inorganic, methylated, and/or glutathionylated arsenic species across cellular membranes are discussed. Furthermore, what is known about arsenic transporters in organs involved in absorption, distribution, and metabolism and how transport pathways contribute to arsenic elimination are described.
authors.affiliation: Department of Physiology and Membrane Protein Disease Research Group, University of Alberta, Edmonton, AB, T6G 2H7, Canada. Electronic address: roggenbe@ualberta.ca.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Roggenbeck
authors.affiliation: Department of Physiology and Membrane Protein Disease Research Group, University of Alberta, Edmonton, AB, T6G 2H7, Canada.
authors.forename: Mayukh
authors.initials: M
authors.lastname: Banerjee
authors.affiliation: Department of Physiology and Membrane Protein Disease Research Group, University of Alberta, Edmonton, AB, T6G 2H7, Canada; Division of Analytical and Environmental Toxicology, Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, T6G 2G3, Canada. Electronic address: eleslie@ualberta.ca.
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Leslie
mesh_terms: D000818:Animals; D001151:Arsenic / Q000378:metabolism*; D001692:Biological Transport; D002273:Carcinogens / Q000378:metabolism*; D006801:Humans; D008322:Mammals / Q000378:metabolism*
chemical_list: D002273:Carcinogens; D001151:Arsenic
keywords: Arsenic; Cellular efflux; Cellular uptake; Glutathione; Transport