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      Polymorphisms in Genes Encoding Potential Mercury Transporters and Urine Mercury Concentrations in Populations Exposed to Mercury Vapor from Gold Mining

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          Abstract

          Background: Elemental mercury (Hg 0) is widely used in small-scale gold mining. Persons working or living in mining areas have high urinary concentrations of Hg (U-Hg). Differences in genes encoding potential Hg-transporters may affect uptake and elimination of Hg.

          Objective: We aimed to identify single nucleotide polymorphisms (SNPs) in Hg-transporter genes that modify U-Hg.

          Methods: Men and women (1,017) from Indonesia, the Philippines, Tanzania, and Zimbabwe were classified either as controls (no Hg exposure from gold mining) or as having low (living in a gold-mining area) or high exposure (working as gold miners). U-Hg was analyzed by cold-vapor atomic absorption spectrometry. Eighteen SNPs in eight Hg-transporter genes were analyzed.

          Results: U-Hg concentrations were higher among ABCC2/ MRP2 rs1885301 A–allele carriers than among GG homozygotes in all populations, though differences were not statistically significant in most cases. MRP2 SNPs showed particularly strong associations with U-Hg in the subgroup with highest exposure (miners in Zimbabwe), whereas rs1885301 A–allele carriers had higher U-Hg than GG homozygotes [geometric mean (GM): 36.4 µg/g creatinine vs. 21.9; p = 0.027], rs2273697 GG homozygotes had higher U-Hg than A–allele carriers (GM: 37.4 vs. 16.7; p = 0.001), and rs717620 A–allele carriers had higher U-Hg than GG homozygotes (GM: 83 vs. 28; p = 0.084). The SLC7A5/ LAT1 rs33916661 GG genotype was associated with higher U-Hg in all populations (statistically significant for all Tanzanians combined). SNPs in SLC22A6/ OAT1 (rs4149170) and SLC22A8/ OAT3 (rs4149182) were associated with U-Hg mainly in the Tanzanian study groups.

          Conclusions: SNPs in putative Hg-transporter genes may influence U-Hg concentrations.

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          Arsenic tolerance in Arabidopsis is mediated by two ABCC-type phytochelatin transporters.

          Arsenic is an extremely toxic metalloid causing serious health problems. In Southeast Asia, aquifers providing drinking and agricultural water for tens of millions of people are contaminated with arsenic. To reduce nutritional arsenic intake through the consumption of contaminated plants, identification of the mechanisms for arsenic accumulation and detoxification in plants is a prerequisite. Phytochelatins (PCs) are glutathione-derived peptides that chelate heavy metals and metalloids such as arsenic, thereby functioning as the first step in their detoxification. Plant vacuoles act as final detoxification stores for heavy metals and arsenic. The essential PC-metal(loid) transporters that sequester toxic metal(loid)s in plant vacuoles have long been sought but remain unidentified in plants. Here we show that in the absence of two ABCC-type transporters, AtABCC1 and AtABCC2, Arabidopsis thaliana is extremely sensitive to arsenic and arsenic-based herbicides. Heterologous expression of these ABCC transporters in phytochelatin-producing Saccharomyces cerevisiae enhanced arsenic tolerance and accumulation. Furthermore, membrane vesicles isolated from these yeasts exhibited a pronounced arsenite [As(III)]-PC(2) transport activity. Vacuoles isolated from atabcc1 atabcc2 double knockout plants exhibited a very low residual As(III)-PC(2) transport activity, and interestingly, less PC was produced in mutant plants when exposed to arsenic. Overexpression of AtPCS1 and AtABCC1 resulted in plants exhibiting increased arsenic tolerance. Our findings demonstrate that AtABCC1 and AtABCC2 are the long-sought and major vacuolar PC transporters. Modulation of vacuolar PC transporters in other plants may allow engineering of plants suited either for phytoremediation or reduced accumulation of arsenic in edible organs.
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            Gender differences in the disposition and toxicity of metals.

            There is increasing evidence that health effects of toxic metals differ in prevalence or are manifested differently in men and women. However, the database is small. The present work aims at evaluating gender differences in the health effects of cadmium, nickel, lead, mercury and arsenic. There is a markedly higher prevalence of nickel-induced allergy and hand eczema in women compared to men, mainly due to differences in exposure. Cadmium retention is generally higher in women than in men, and the severe cadmium-induced Itai-itai disease was mainly a woman's disease. Gender differences in susceptibility at lower exposure are uncertain, but recent data indicate that cadmium has estrogenic effects and affect female offspring. Men generally have higher blood lead levels than women. Lead accumulates in bone and increased endogenous lead exposure has been demonstrated during periods of increased bone turnover, particularly in women in pregnancy and menopause. Lead and mercury, in the form of mercury vapor and methylmercury, are easily transferred from the pregnant women to the fetus. Recent data indicate that boys are more susceptible to neurotoxic effects of lead and methylmercury following exposure early in life, while experimental data suggest that females are more susceptible to immunotoxic effects of lead. Certain gender differences in the biotransformation of arsenic by methylation have been reported, and men seem to be more affected by arsenic-related skin effect than women. Experimental studies indicate major gender differences in arsenic-induced cancer. Obviously, research on gender-related differences in health effects caused by metals needs considerable more focus in the future.
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              Molecular and ionic mimicry and the transport of toxic metals.

              Despite many scientific advances, human exposure to, and intoxication by, toxic metal species continues to occur. Surprisingly, little is understood about the mechanisms by which certain metals and metal-containing species gain entry into target cells. Since there do not appear to be transporters designed specifically for the entry of most toxic metal species into mammalian cells, it has been postulated that some of these metals gain entry into target cells, through the mechanisms of ionic and/or molecular mimicry, at the site of transporters of essential elements and/or molecules. The primary purpose of this review is to discuss the transport of selective toxic metals in target organs and provide evidence supporting a role of ionic and/or molecular mimicry. In the context of this review, molecular mimicry refers to the ability of a metal ion to bond to an endogenous organic molecule to form an organic metal species that acts as a functional or structural mimic of essential molecules at the sites of transporters of those molecules. Ionic mimicry refers to the ability of a cationic form of a toxic metal to mimic an essential element or cationic species of an element at the site of a transporter of that element. Molecular and ionic mimics can also be sub-classified as structural or functional mimics. This review will present the established and putative roles of molecular and ionic mimicry in the transport of mercury, cadmium, lead, arsenic, selenium, and selected oxyanions in target organs and tissues.
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                Author and article information

                Journal
                Environ Health Perspect
                Environ. Health Perspect
                EHP
                Environmental Health Perspectives
                National Institute of Environmental Health Sciences
                0091-6765
                1552-9924
                09 October 2012
                January 2013
                : 121
                : 1
                : 85-91
                Affiliations
                [1 ]Department of Laboratory Medicine, Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden
                [2 ]United Nations Industrial Development Organization, Vienna, Austria
                [3 ]Institute of Forensic Medicine, Ludwig Maximilians University, Munich, Germany
                [4 ]Institute of Public Health, Medical Decision Making and Health Technology Assessment, UMIT–University for Health Sciences, Medical Informatics and Technology, Hall in Tirol, Austria
                [5 ]Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, University Hospital Munich, Munich, Germany
                Author notes
                Address correspondence to K. Engström, Occupational and Environmental Medicine, Lund University Hospital, SE-22185 Lund, Sweden. Telephone: 46 (0) 46 173135. Fax: 46 (0) 46 143702. E-mail: karin.engstrom@ 123456med.lu.se
                Article
                ehp.1204951
                10.1289/ehp.1204951
                3553430
                23052037
                83c8e831-d1fd-49a1-a7d0-279b574adba2
                Copyright @ 2013

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, properly cited.

                History
                : 11 January 2012
                : 09 October 2012
                Categories
                Research

                Public health
                gold mining,inorganic mercury,lat1,mdr1,mrp1,oat1,oat3,slc3a2,slc22a6,slc22a8
                Public health
                gold mining, inorganic mercury, lat1, mdr1, mrp1, oat1, oat3, slc3a2, slc22a6, slc22a8

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