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Chemical, Biochemical, and Genetic Approaches to Arsenic Metabolism" -An overview of arsenic metabolism and toxicity- A series of five papers to appear together in Current Protocols in Toxicology
Citation:
Hernandez-Zavala, A., Z. Drobna, M. Styblo, AND D. J. THOMAS. Chemical, Biochemical, and Genetic Approaches to Arsenic Metabolism" -An overview of arsenic metabolism and toxicity- A series of five papers to appear together in Current Protocols in Toxicology. Current Protocols in Toxicology. Wiley InterScience, Silver Spring, MD, 42(4.33):1-4, (2009).
Impact/Purpose:
These five ms describes various chemical, biochemical, and genetic techniques which are applied to the study of arsenic metabolism in in vitro systems, cultured cells, and intact organisms.
Description:
The toxic properties of arsenic (As) were recognized long before Albertus Magnus in the 13th century prepared its elemental form (Buchanan, 1962). Its use as a poison has played lethal and decisive roles in domestic and dynastic intrigues throughout history (Cullen, 2008). Inorganic As (iAs) remained a mainstay of the poisoner's art until methods for its detection were developed in the 19th century (Jolliffe, 1993). The potency of As as a carcinogen in humans has also been apparent since the beginning of its use in industrial processes. Studies in workers exposed to iAs as arsenite (iAsIII) or arsenate (iAsv) have found increased prevalences of various internal cancers (Enterline et aI., 1995; Lubin et aI., 2000). In addition, arsenicals have a long history of medicinal use. Fowler's solution (an alcoholic solution of potassium arsenite) was widely used for several centuries as a tonic for dermatological, hematological, and respiratory ailments. Synthesis of Salvarsan (arsenphenamine, compound 606) by Paul Ehrlich and its use as a treatment for syphilis marked the beginning of modern chemotherapeutics (Schwarz, 2004). Organoarsenicals were widely used as antibiotics until the 1940s when they were displaced by sulfa drugs or penicillin and other microbial antibiotics. In recent years, iAs as arsenic trioxide has returned to the therapeutic armamentarium as a treatment for acute promyelocytic leukemia (Douer and Tallman, 2005). In the past half century, iAs has emerged as a significant environmental contaminant. Exposure to iAs as a contaminant of drinking water was first recognized as a major public health problem in Taiwan. In certain regions of that island, individuals who chronically consumed drinking water containing iAs displayed a range of skin and vascular lesions that were attributed to As exposure (Tseng et aI., 1968; Tseng, 1977). Studies in Taiwan and elsewhere have demonstrated that chronic exposure is associated with increased risk of vascular disease, diabetes, and internal cancers (Smith et aI., 1992; Navas-Acien et al., 2005, 2008; Chen et al., 2007; Wang et aI., 2007). Through the years, other populations elsewhere in the world have also been identified as chronic users of drinking water supplies that are contaminated with iAs. There is abundant evidence of adverse health effects in all of these populations. Indeed, the plight of tens of millions of individuals exposed to iAs in Bangladesh and West Bengal has been described as a "public health emergency" (Smith et al., 2000) and as "the largest poisoning of a population in history" (Bhattacharjee, 2007), assessments that are difficult to discount given the number ofaffected individuals. Given the strong epidemiological evidence of myriad adverse health effects that are attributable to chronic exposure to iAs, there has been a growing interest in understanding of the distribution and metabolism of this metalloid in humans. Coupled with a renewed interest in potential modes of actions of arsenicals as toxicants or carcinogens, this has lead to a rapid expansion of our knowledge in these fields. In this chapter, attention is devoted to the study of metabolism of As in in vitro assays and in cultured cells. In particular, the enzymatic basis of As methylation is considered. In the following paragraphs, we provide a brief summary of current models for the biological methylation of arsenicals. The nomenclature for arsenicals used here follows common usage in the toxicological literature. Because the oxidation state of arsenic in various compounds is of interest, this distinction is indicated in the naming of compounds. Systematic names and abbreviations used for arsenicals: arsenite (arsenous acid) AsIII(OH)3, iAsIII; arsenate (arsenic acid) Asv(O)(OH)3, iAsv; (mono) methylarsonous acid CH3Aslll(OH)2 MAsIII; (mono)methylarsonic acid CH3Asv(O)(OH)2, MAsv;; dimethylarsinous acid (CH3)2, AsIIIOH, DMAsIII; .dimethylarsinic acid (CH3)2 Asv(O)OH, DMAsV: trimethylarsine oxide, (CH3)3Asv(O). TMAO. In cases where the oxidation state of arsenic cannot be determined or is not germane, the generic abbreviations iAs, MAs, and DMAs are used.