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      Urinary Arsenic Metabolites of Subjects Exposed to Elevated Arsenic Present in Coal in Shaanxi Province, China

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          Abstract

          In contrast to arsenic (As) poisoning caused by naturally occurring inorganic arsenic-contaminated water consumption, coal arsenic poisoning (CAP) induced by elevated arsenic exposure from coal combustion has rarely been reported. In this study, the concentrations and distributions of urinary arsenic metabolites in 57 volunteers (36 subjects with skin lesions and 21 subjects without skin lesions), who had been exposed to elevated levels of arsenic present in coal in Changshapu village in the south of Shaanxi Province (China), were reported. The urinary arsenic species, including inorganic arsenic (iAs) [arsenite (iAs III) and arsenate (iAs V)], monomethylarsonic acid (MMA V) and dimethylarsinic acid (DMA V), were determined by high-performance liquid chromatography (HPLC) combined with inductively coupled plasma mass spectroscopy (ICP-MS). The relative distributions of arsenic species, the primary methylation index (PMI = MMA V/iAs) and the secondary methylation index (SMI = DMA V/MMA V) were calculated to assess the metabolism of arsenic. Subjects with skin lesions had a higher concentration of urinary arsenic and a lower arsenic methylation capability than subjects without skin lesions. Women had a significantly higher methylation capability of arsenic than men, as defined by a higher percent DMA V and SMI in urine among women, which was the one possible interpretation of women with a higher concentration of urinary arsenic but lower susceptibility to skin lesions. The findings suggested that not only the dose of arsenic exposure but also the arsenic methylation capability have an impact on the individual susceptibility to skin lesions induced by coal arsenic exposure.

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          Most cited references53

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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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            Mechanisms of arsenic biotransformation.

            Inorganic arsenic, a documented human carcinogen, is methylated in the body by alternating reduction of pentavalent arsenic to trivalent and addition of a methyl group from S-adenosylmethionine. Glutathione, and possibly other thiols, serve as reducing agents. The liver is the most important site of arsenic methylation, but most organs show arsenic methylating activity. The end metabolites are methylarsonic acid (MMA) and dimethylarsinic acid (DMA). These are less reactive with tissue constituents than inorganic arsenic and readily excreted in the urine. However, reactive intermediates may be formed. Absorbed arsenate (As(V)) is fairly rapidly reduced in blood to As(III), which implies increased toxicity. Also, intermediate reduced forms of the methylated metabolites, MMA(III) and DMA(III), have been detected in human urine. In particular MMA(III) is highly toxic. To what extent MMA(III) and DMA(III) contribute to the observed toxicity following exposure to inorganic arsenic remains to be elucidated. There are marked differences in the metabolism of arsenic between mammalian species, population groups and individuals. There are indications that subjects with low MMA in urine have faster elimination of ingested arsenic, compared to those with more MMA in urine.
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              Monomethylarsonous acid (MMA(III)) is more toxic than arsenite in Chang human hepatocytes.

              Methylation has been considered to be the primary detoxication pathway of inorganic arsenic. Inorganic arsenic is methylated by many, but not all animal species, to monomethylarsonic acid (MMA(V)), monomethylarsonous acid (MMA(III)), and dimethylarsinic acid (DMA(V)). The As(V) derivatives have been assumed to produce low toxicity, but the relative toxicity of MMA(III) remains unknown. In vitro toxicities of arsenate, arsenite, MMA(V), MMA(III), and DMA(V) were determined in Chang human hepatocytes. Leakage of lactate dehydrogenase (LDH) and intracellular potassium (K(+)) and mitochondrial metabolism of the tetrazolium salt XTT were used to assess cytotoxicity due to arsenic exposure. The mean LC50 based on LDH assays in phosphate media was 6 microM for MMA(III) and 68 microM for arsenite. Using the assay for K(+) leakage in phosphate media, the mean LC50 was 6.3 microM for MMA(III) and 19.8 microM for arsenite. The mean LC50 based on the XTT assay in phosphate media was 13.6 microM for MMA(III) and 164 microM for arsenite. The results of the three cytotoxicity assays (LDH, K(+), and XTT) reveal the following order of toxicity in Chang human hepatocytes: MMA(III) > arsenite > arsenate > MMA(V) = DMA(V). Data demonstrate that MMA(III), an intermediate in inorganic arsenic methylation, is highly toxic and again raises the question as to whether methylation of inorganic arsenic is a detoxication process. Copyright 2000 Academic Press.
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                Author and article information

                Journal
                Int J Environ Res Public Health
                101238455
                International Journal of Environmental Research and Public Health
                Molecular Diversity Preservation International (MDPI)
                1661-7827
                1660-4601
                June 2011
                3 June 2011
                : 8
                : 6
                : 1991-2008
                Affiliations
                [1 ] Institute of Geographical Sciences and Natural Resources Research, Chinese Academy of Sciences, 11A Datun Road, Beijing 100101, China; E-Mails: gaojw.06b@ 123456igsnrr.ac.cn (J.G.); yujp@ 123456igsnrr.ac.cn (J.Y.)
                [2 ] Graduate School of the Chinese Academy of Sciences, Beijing 10049, China
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: yangls@ 123456igsnrr.ac.cn ; Tel.: +86-10-6488-9060; Fax: +86-10-6485-6504.
                Article
                ijerph-08-01991
                10.3390/ijerph8061991
                3138009
                21776214
                246e23ed-0854-4fe3-a2d5-d65de2321f9e
                © 2011 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 14 April 2011
                : 26 May 2011
                : 30 May 2011
                Categories
                Article

                Public health
                skin lesions,urinary metabolites,methylation capability,arsenic (as),china,coal arsenic poisoning (cap)

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