An overview on chronic arsenism via drinking water in PR China

Chronic endemic arsenism via drinking water was first found in Taiwan in 1968, and reported in Xinjiang Province in mainland China in the 1980s. Arsenism has become one of the most serious endemic diseases in China in the last two decades. Up to now, the disease has been found in Inner Mongolia, Shanxi, Ningxia, Jilin and Qinghai provinces. According to the Chinese maximum limit standard of arsenic (As) in drinking water, over 2 millions people have been exposed to high arsenic and about 10,000 persons were diagnosed as arsenism patients. There are different As concentrations in the water of different sites, even in the same area. Most of the As concentrations range from 0.05 to 2.0mg/l. The incidence of arsenism increases as As concentrations in drinking water and the drinking time increase. The age distribution of patients with arsenism ranged from 3 to 80 years old with peak prevalence in adults. A dose-effect relationship between the status of arsenism and arsenic level and drinking time has been shown. New high-arsenic areas in China have been discovered during recent investigations. In order to reduce the adverse health effects of arsenism, the central and local governments of China have provided significant funds to change water levels of As and at the same time take general measures to "reduce arsenic intake, remove arsenic from the body and treat the patients". After the implementation of these control measures in certain regions, the clinical symptoms and signs of 30% of the patients were improved. There was no change in 52% of patients and only 18% of patients got worse. It is suggested that future work in the research and control of arsenism in China should include: (1) identify all the high arsenic areas in China, (2) study the association of arsenism with fluorosis, (3) determine individual susceptibility, (4) select biomarkers for diagnosis in the early stage of a arsenism, and (5) investigate the molecular mechanisms of carcinogenesis.     

Residential exposure to drinking water arsenic in Inner Mongolia, China

In the Ba Men region of Inner Mongolia, China, a high prevalence of chronic arsenism has been reported in earlier studies. A survey of the arsenic contamination among wells from groundwater was conducted to better understand the occurrence of arsenic (As) in drinking water. A total of 14,866 wells (30% of all wells in the region) were analyzed for their arsenic-content. Methods used to detect arsenic were Spectrophotometric methods with DCC-Ag (detection limit, 0.5 microg of As/L); Spot method (detection limit, 10 microg of As/L); and air assisted Colorimetry method (detection limit, 20 microg of As/L). Arsenic-concentrations ranged from below limit of detection to 1200 microg of As/L. Elevated concentrations were related to well depth (10 to 29 m), the date the well was built (peaks from 1980-1990), and geographic location (near mountain range). Over 25,900 individuals utilized wells with drinking water arsenic concentrations above 20 microg of As/L (14,500 above 50 microg of As/L-the current China national standard in drinking water and 2198 above 300 microg of As/L). The presented database of arsenic in wells of the Ba Men region provides a useful tool for planning future water explorations when combined with geological information as well as support for designing upcoming epidemiological studies on the effects of arsenic in drinking water for this region.     

Analyses of micronuclei in exfoliated epithelial cells from individuals chronically exposed to arsenic via drinking water in inner Mongolia, China.

The groundwater in Bayingnormen (Ba Men), located in Central West Inner Mongolia, China, is naturally contaminated with arsenic at concentrations ranging from 50 microg/L to 1.8 mg/L. Various adverse health effects in this region, including cancer, have been linked to arsenic exposure via drinking water. A pilot study was undertaken to evaluate frequencies of micronuclei (MN), as measures of chromosomal alterations, in multiple exfoliated epithelial cell types from residents of Ba Men chronically exposed to arsenic via drinking water. Buccal mucosal cells, airway epithelial cells in sputum, and bladder urothelial cells were collected from 19 residents exposed to high levels of arsenic in drinking water (527.5 +/- 24 microg/l), and from 13 control residents exposed to relatively low levels of arsenic in drinking water (4.4 +/- microg/L). Analytical results from these individuals revealed that MN frequencies in the high-exposure group were significantly elevated to 3.4-fold over control levels for buccal and sputum cells, and to 2.7-fold over control for bladder cells (increases in MN frequency significant at p < .001 for buccal cells; p < .01 for sputum cells; p < .05 for bladder cells). When smokers were excluded from high-exposure and control groups the effects of arsenic were observed to be greater, although only in buccal and sputum cells; approximately 6-fold increases in MN frequency occurred in these tissues. The results indicate that residents of Ba Men chronically exposed to high levels of arsenic in drinking water reveal evidence of genotoxicity in multiple epithelial cell types; higher levels of induced MN were observed in buccal and sputum cells than in bladder cells.     

Effect of environmental exposure of arsenic on cattle and poultry in nadia district, west bengal, India

A study was undertaken to evaluate an alternative source of arsenicosis in human food chain through livestock. Thirty milch cattle and 20 poultry birds along with their eggs were selected randomly from two endemic villages of Nadia district and one nonendemic villages of Hooghly district in West Bengal, India. Milk, feces, urine, and hair samples of cattle and feed materials, such as water and straw, were collected to analyze arsenic status. Arsenic concentration in egg yolk and albumen from poultry eggs and different poultry organs after culling was estimated. Distribution of arsenic in animal body indicates that major portion of arsenic was eliminated through feces, urine, and milk. Poultry egg yolk, albumen, and poultry products retain arsenic in all organs. Cows and poultry birds reared in endemic zone retain significantly higher concentration of arsenic. Consumption of egg, agricultural produces grown in contaminated soil, and milk might have produced arsenicosis and may be considered as alternative source of arsenic contamination.     

Evaluation of the serum catalase and myeloperoxidase activities in chronic arsenic-exposed individuals and concomitant cytogenetic damage

Chronic arsenic exposure through contaminated drinking water is a major environmental health issue. Chronic arsenic exposure is known to exert its toxic effects by a variety of mechanisms, of which generation of reactive oxygen species (ROS) is one of the most important. A high level of ROS, in turn, leads to DNA damage that might ultimately culminate in cancer. In order to keep the level of ROS in balance, an array of enzymes is present, of which catalase (CAT) and myeloperoxidase (MPO) are important members. Hence, in this study, we determined the activities of these two enzymes in the sera and chromosomal aberrations (CA) in peripheral blood lymphocytes in individuals exposed and unexposed to arsenic in drinking water. Arsenic in drinking water and in urine was used as a measure of exposure. Our results show that individuals chronically exposed to arsenic have significantly higher CAT and MPO activities and higher incidence of CA. We found moderate positive correlations between CAT and MPO activities, induction of CA and arsenic in urine and water. These results indicate that chronic arsenic exposure causes higher CAT and MPO activities in serum that correlates with induction of genetic damage. We conclude that the serum levels of these enzymes might be used as biomarkers of early arsenic exposure induced disease much before the classical dermatological symptoms of arsenicosis begin to appear.     

Urinary porphyrins as biomarkers for arsenic exposure among susceptible populations in Guizhou province, China

Coal is widely used in PR China. Unfortunately, coal from some areas in Guizhou Province contains elevated levels of arsenic. This has caused arsenicosis in individuals who use arsenic-contaminated coal for the purposes of heating, cooking and drying of food in poorly ventilated dwellings. The population at risk has been estimated to be approximately 200,000 people. Clinical symptoms of arsenicosis may include changes of skin pigmentation, hyperkeratosis of hand and feet, skin cancers, liver damage, persistent cough and chronic bronchitis. We analyzed the porphyrin excretion profile using a HPLC method in urine samples collected from 113 villagers who lived in Xing Ren district, a coal-borne arsenicosis endemic area and from 30 villagers from Xing Yi where arsenicosis is not prevalent. Urinary porphyrins were higher in the arsenic exposed group than those in the control group. The correlation between urinary arsenic and porphyrin concentrations demonstrated the effect of arsenic on heme biosynthesis resulting in increased porphyrin excretion. Both uroporphyrin and coproporphyrin III showed significant increases in the excretion profile of the younger age (<20 years) arsenic-exposed group, suggesting that porphyrins could be used as early warning biomarkers of chronic arsenic exposure in humans. Greater increases of urinary arsenic and porphyrins in women, children and older age groups who spend much of their time indoors suggest that they might be at a higher risk. Whether elevated porphyrins could predict adverse health effects associated with both cancer and non-cancer end-points in chronically arsenic-exposed populations need further investigation.     

Changes in serum thioredoxin among individuals chronically exposed to arsenic in drinking water

It is well known that oxidative damage plays a key role in the development of chronic arsenicosis. There is a complex set of mechanisms of redox cycling in vivo to protect cells from the damage. In this study, we examined the differences in the levels of serum thioredoxin1 (TRX1) among individuals exposed to different levels of arsenic in drinking water and detected early biomarkers of arsenic poisoning before the appearance of skin lesions. A total of 157 subjects from endemic regions of China were selected and divided into arsenicosis group with skin lesions (total intake of arsenic: 8.68-45.71 mg-year) and non-arsenicosis group without skin lesions, which further divided into low (0.00-1.06 mg-year), medium (1.37-3.55 mg-year), and high (4.26-48.13 mg-year) arsenic exposure groups. Concentrations of serum TRX1 were analyzed by an ELISA method. Levels of water arsenic and urinary speciated arsenics, including inorganic arsenic (iAs), monomethylated arsenic (MMA), and dimethylated arsenic (DMA), were determined by hydride generation atomic absorption spectrometry. Our results showed that the levels of serum TRX1 in arsenicosis patients were significantly higher than that of the subjects who were chronically exposed to arsenic, but without skin lesions. A positive correlation was seen between the levels of serum TRX1 and the total water arsenic intake or the levels of urinary arsenic species. The results of this study indicate that arsenic exposure could significantly change the levels of human serum TRX1, which can be detected before arsenic-specific dermatological symptoms occur. This study provides further evidence on revealing the mechanism of arsenic toxicity.     

Enhanced carcinogenicity by coexposure to arsenic and iron and a novel remediation system for the elements in well drinking water

Various carcinomas including skin cancer are explosively increasing in arsenicosis patients who drink arsenic-polluted well water, especially in Bangladesh. Although well drinking water in the cancer-prone areas contains various elements, very little is known about the effects of elements except arsenic on carcinogenicity. In order to clarify the carcinogenic effects of coexposure to arsenic and iron, anchorage-independent growth and invasion in human untransformed HaCaT and transformed A431 keratinocytes were examined. Since the mean ratio of arsenic and iron in well water was 1:10 in cancer-prone areas of Bangladesh, effects of 1 μM arsenic and 10 μM iron were investigated. Iron synergistically promoted arsenic-mediated anchorage-independent growth in untransformed and transformed keratinocytes. Iron additionally increased invasion in both types of keratinocytes. Activities of c-SRC and ERK that regulate anchorage-independent growth and invasion were synergistically enhanced in both types of keratinocytes. Our results suggest that iron promotes arsenic-mediated transformation of untransformed keratinocytes and progression of transformed keratinocytes. We then developed a low-cost and high-performance adsorbent composed of a hydrotalcite-like compound for arsenic and iron. The adsorbent rapidly reduced concentrations of both elements from well drinking water in cancer-prone areas of Bangladesh to levels less than those in WHO health-based guidelines for drinking water. Thus, we not only demonstrated for the first time increased carcinogenicity by coexposure to arsenic and iron but also proposed a novel remediation system for well drinking water.     

Drinking water arsenic exposure and blood pressure in healthy women of reproductive age in Inner Mongolia, China

The extremely high exposure levels evaluated in prior investigations relating elevated levels of drinking water arsenic and hypertension prevalence make extrapolation to potential vascular effects at lower exposure levels very difficult. A cross-sectional study was conducted on 8790 women who had recently been pregnant in an area of Inner Mongolia, China known to have a gradient of drinking water arsenic exposure. This study observed increased systolic blood pressure levels with increasing drinking water arsenic, at lower exposure levels than previously reported in the literature. As compared to the referent category (below limit of detection to 20 microg of As/L), the overall population mean systolic blood pressure rose 1.29 mm Hg (95% CI 0.82, 1.75), 1.28 mm Hg (95% CI 0.49, 2.07), and 2.22 mm Hg (95% CI 1.46, 2.97) as drinking water arsenic concentration increased from 21 to 50, 51 to 100, and >100 microg of As/L, respectively. Controlling for age and body weight (n=3260), the population mean systolic blood pressure rose 1.88 mm Hg (95% CI 1.03, 2.73), 3.90 mm Hg (95% CI 2.52, 5.29), and 6.83 mm Hg (95% CI 5.39, 8.27) as drinking water arsenic concentration increased, respectively. For diastolic blood pressure effect, while statistically significant, was not as pronounced as systolic blood pressure. Mean diastolic blood pressure rose 0.78 mm Hg (95% CI 0.39, 1.16), 1.57 mm Hg (95% CI 0.91, 2.22) and 1.32 mm Hg (95% CI 0.70, 1.95), respectively, for the overall population and rose 2.11 mm Hg (95% CI 1.38, 2.84), 2.74 mm Hg (95% CI 1.55, 3.93), and 3.08 mm Hg (95% CI 1.84, 4.31), respectively, for the adjusted population (n=3260) at drinking water arsenic concentrations of 21 to 50, 51 to 100, and >100 microg of As/L. If our study results are confirmed in other populations, the potential burden of cardiovascular disease attributable to drinking water arsenic is significant.     

Effect of chronic intake of arsenic-contaminated water on liver

The hepatotoxic effect of arsenic when used in therapeutic dose has long been recognized. We described the nature and degree of liver involvement and its pathogenesis due to prolonged drinking of arsenic-contaminated water in West Bengal, India. From hospital-based studies on 248 cases of arsenicosis, hepatomegaly was found in 190 patients (76.6%). Non cirrhotic portal fibrosis was the predominant lesions in 63 out of 69 cases who underwent liver biopsy. The portal fibrosis was characterized by expansion of portal zones with streaky fibrosis, a few of which contained leash of vessels. However, portal hypertension was found in smaller number of cases. A cross-sectional epidemiological study was carried out on 7683 people residing in arsenic-affected districts of West Bengal. Out of these, 3467 and 4216 people consumed water-containing arsenic below and above 0.05 mg/l, respectively. Prevalence of hepatomegaly was significantly higher in arsenic-exposed people (10.2%) compared to controls (2.99%, P < 0.001). The incidence of hepatomegaly was found to have a linear relationship proportionate to increasing exposure of arsenic in drinking water in both sexes (P < 0.001). In an experimental study, BALB/C mice were given water contaminated with arsenic (3.2 mg/l) ad libitum for 15 months, the animals being sacrificed at 3-month intervals. We observed progressive reduction of hepatic glutathione and enzymes of anti-oxidative defense system associated with lipid peroxidation. Liver histology showed fatty infiltration at 12 months and hepatic fibrosis at 15 months. Our studies show that prolong drinking of arsenic-contaminated water is associated with hepatomegaly. Predominant lesion of hepatic fibrosis appears to be caused by arsenic induced oxystress.     

贵州省实施燃煤污染型砷中毒综合防制项目效果评估

目的评价采取综合措施控制贵州省燃煤型地方性砷中毒(地砷病)病区砷污染的效果。方法实施以健康教育为基础,禁止开采高砷煤和改良炉灶为主的综合防治措施后,采取随机抽样的方法对其效果进行评估。结果通过强有力的健康促进,在病区,砷中毒防治知识家喻户晓,深入人心;高砷煤开采得到基本禁止;全部家庭用上了有排烟设施的炉灶,炉灶正确使用率达到90%;家庭玉米和辣椒正确干燥率均达到90%以上;大多数家庭已经养成烹调前淘洗食物的习惯,有效的将煤烟排出室外,基本避免了玉米和辣椒等食物污染,减少了砷的摄入量,机体尿砷排泄显著减少,接近正常人排泄水平。结论在地砷病区实施综合控制措施取得预期成效。     

Arsenic methylation capacity and its correlation with skin lesions induced by contaminated drinking water consumption in residents of chronic arsenicosis area

Chronic exposure to excess level of arsenic through contaminated drinking water is associated with many injuries, among which skin lesions are the most prominent. In this study, we measured the concentrations of inorganic arsenic (iAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) in the blood of the residents of arsenicosis area, who demonstrated different skin lesion grade from mild, moderate to advanced. We evaluated the individual methylation capacity by two indices of the first and secondary methylation ratio (FMR and SMR). We found that SMR of moderate and advanced groups were markedly lower than that of mild group. Significant negative correlation was found between SMR of all the subjects and the grade of skin lesion, with Spearman's correlation coefficient of ?0.429 (P = 0.016). Moreover, blood MMA proportion of moderate and advanced groups was found to be significantly higher than that of the mild group. These results suggest that low secondary arsenic methylation capacity and high MMA proportion are associated with the severity of arsenic‐related skin lesions. Our findings evaluated by blood speciation is consistent with that evaluated by the generally accepted urinary arsenic speciation in the relationship between arsenic methylation capacity and arsenic‐related lesions. © 2009 Wiley Periodicals, Inc. Environ Toxicol 26: 118–123, 2011.     

Long-term arsenic exposure and ischemic heart disease in arseniasis-hyperendemic villages in Taiwan

The association between long-term arsenic exposure and peripheral vascular disease has been well documented in our previous epidemiologic studies. The purpose of this study was to evaluate whether long-term arsenic exposure could be associated with ischemic heart disease (IHD). A total of 462 subjects living in the blackfoot disease-hyperendemic villages along the southwestern coast of Taiwan and characterized by long-term arsenic exposure from drinking artesian well water was studied. The subjects were recruited from an epidemiologic cohort who participated in a health examination. IHD was diagnosed by coding the resting electrocardiograms with the Minnesota code. History of arsenic exposure was estimated through information obtained from a personal interview according to a structured questionnaire and the arsenic content in artesian well water of the villages. Cumulative arsenic exposure (CAE) was calculated as the sum of the products multiplying the arsenic concentration in artesian well water (mg/l) by the duration of drinking the water (years) in consecutive periods of living in the different villages. Among the subjects, 78 cases (16.9%) were diagnosed as having IHD. The prevalence rates of IHD for the age groups of 30-39, 40-49, 50-59, and >/=60 years were 4.9, 7.5, 16.8, and 30.7%, respectively (P<0.001). For those with CAE of 0, 0.1-14.9 and >/=15 mg/l-years, the prevalence rates of IHD were 5.2, 10.9 and 24.1%, respectively (P<0.001). The odds ratios (95% confidence intervals) for IHD were 1.60 (0.48, 5.34), and 3.60 (1.11, 11.65), respectively, for those with CAE of 0.1-14.9 and >/=15.0 mg/l-years, when compared with those lacking drinking water exposure to arsenic after multivariate adjustment. It is concluded that IHD in the arseniasis-hyperendemic villages in Taiwan was associated with long-term arsenic exposure.     

Toxicology and Genetic Susceptibility of Drugs and Pollutant

S21Possibleinvolvementofhereditaryfactors intheriskmodulationofarseniasisintwoethnic clansexposedtoindoorcombustionofhigharse niccoal LINGuo Fang1,DUHui2,CHENJi Gang3,LU Hong Chao2,GUOWei Chao1,ZHANGXin Jiang4,SHENJian Hua1(1.ShanghaiInstituteforBiologicalSciences,Institute ofPlantPhysiologyandEcology,ChineseAcademyof Sciences,Shanghai200032,China;2.Prefecture CenterforDiseasePreventionandControl,Guiyang562400,China;3.MunicipalCenterforDiseasePre ventionandControl,Shang…     

Chronic arsenic toxicity in Bangladesh and West Bengal, India--a review and commentary.

Fifty districts of Bangladesh and 9 districts in West Bengal, India have arsenic levels in groundwater above the World Health Organization's maximum permissible limit of 50 microg/L. The area and population of 50 districts of Bangladesh and 9 districts in West Bengal are 118,849 km2 and 104.9 million and 38,865 km2 and 42.7 million, respectively. Our current data show arsenic levels above 50 microg/ L in 2000 villages, 178 police stations of 50 affected districts in Bangladesh and 2600 villages, 74 police stations/blocks of 9 affected districts in West Bengal. We have so far analyzed 34,000 and 101,934 hand tube-well water samples from Bangladesh and West Bengal respectively by FI-HG-AAS of which 56% and 52%, respectively, contained arsenic above 10 microg/L and 37% and 25% arsenic above 50 microg/L. In our preliminary study 18,000 persons in Bangladesh and 86,000 persons in West Bengal were clinically examined in arsenic-affected districts. Of them, 3695 (20.6% including 6.11% children) in Bangladesh and 8500 (9.8% including 1.7% children) in West Bengal had arsenical dermatological features. Symptoms of chronic arsenic toxicity developed insidiously after 6 months to 2 years or more of exposure. The time of onset depends on the concentration of arsenic in the drinking water, volume of intake, and the health and nutritional status of individuals. Major dermatological signs are diffuse or spotted melanosis, leucomelanosis, and keratosis. Chronic arsenicosis is a multisystem disorder. Apart from generalized weakness, appetite and weight loss, and anemia, our patients had symptoms relating to involvement of the lungs, gastrointestinal system, liver, spleen, genitourinary system, hemopoietic system, eyes, nervous system, and cardiovascular system. We found evidence of arsenic neuropathy in 37.3% (154 of 413 cases) in one group and 86.8% (33 of 38 cases) in another. Most of these cases had mild and predominantly sensory neuropathy. Central nervous system involvement was evident with and without neuropathy. Electrodiagnostic studies proved helpful for the diagnosis of neurological involvement. Advanced neglected cases with many years of exposure presented with cancer of skin and of the lung, liver, kidney, and bladder. The diagnosis of subclinical arsenicosis was made in 83%, 93%, and 95% of hair, nail and urine samples, respectively, in Bangladesh; and 57%, 83%, and 89% of hair, nail, and urine samples, respectively in West Bengal. Approximately 90% of children below 11 years of age living in the affected areas show hair and nail arsenic above the normal level. Children appear to have a higher body burden than adults despite fewer dermatological manifestations. Limited trials of 4 arsenic chelators in the treatment of chronic arsenic toxicity in West Bengal over the last 2 decades do not provide any clinical, biochemical, or histopathological benefit except for the accompanying preliminary report of clinical benefit with dimercaptopropanesulfonate therapy. Extensive efforts are needed in both countries to combat the arsenic crisis including control of tube-wells, watershed management with effective use of the prodigious supplies of surface water, traditional water management, public awareness programs, and education concerning the apparent benefits of optimal nutrition.     

Structure-function alteration of hemoglobin in arsenicosis patients: a probable pathway to exert toxicity

Chronic arsenicosis, a major public health concern in India and Bangladesh, is mainly caused by ingestion of arsenic (As) contaminated ground water. Although this problem has been studied extensively, the mechanism of toxicity remains unknown. This paper investigates the process of trivalent arsenicals binding to hemoglobin (Hb) in chronic arsenicosis patients and consequent modification in the structure–function activity of Hb. In this work peroxidase activity, thermal denaturation profile, oxygen releasing capacity and hydrodynamic diameter have been evaluated for the Hb collected from subjects suffering with chronic arsenicosis. Increased peroxidative activity suggests altered oxidative status of Hb in the diseased state. The thermal denaturation profile indicates the Hb molecule to be more susceptible to unfolding in the pathologic state. The enhanced oxygen releasing capacity and significant reduction in hydrodynamic diameter of Hb is also observed in the diseased condition, suggesting conformational alterations in the Hb molecule. Finally, trivalent arsenic is found to bind with freshly isolated Hb from arsenicosis patients, binding affinity constant being 0.256 μM^?1. The binding is positively cooperative with a Hill coefficient of +2.961 and isosbestic points at specific wavelengths. Thus, our work explores the structure–function property of Hb in chronic arsenicosis subjects and reveals that the molecule is modified in such a way that comparatively weak binding with oxygen and strong binding with arsenic occur simultaneously. This association may play a crucial role in exerting the pathway for arsenic toxicity. Copyright © 2011 John Wiley & Sons, Ltd.     

Arsenic induces apoptosis in mouse liver is mitochondria dependent and is abrogated by N-acetylcysteine

Arsenicosis, caused by arsenic contamination of drinking water supplies, is a major public health problem in India and Bangladesh. Chronic liver disease, often with portal hypertension occurs in chronic arsenicosis, contributes to the morbidity and mortality. The early cellular events that initiate liver cell injury due to arsenicosis have not been studied. Our aim was to identify the possible mechanisms related to arsenic-induced liver injury in mice. Liver injury was induced in mice by arsenic treatment. The liver was used for mitochondrial oxidative stress, mitochondrial permeability transition (MPT). Evidence of apoptosis was sought by TUNEL test, caspase assay and histology. Pretreatment with N-acetyl-L-cysteine (NAC) was done to modulate hepatic GSH level. Arsenic treatment in mice caused liver injury associated with increased oxidative stress in liver mitochondria and alteration of MPT. Altered MPT facilitated cytochrome c release in the cytosol, activation of caspase 9 and caspase 3 activities and apoptotic cell death. Pretreatment of NAC to arsenic-treated mice abrogated all these alteration suggesting a glutathione (GSH)-dependent mechanism. Oxidative stress in mitochondria and inappropriate MPT are important in the pathogenesis of arsenic induced apoptotic liver cell injury. The phenomenon is GSH dependent and supplementation of NAC might have beneficial effects.     

Oxidative DNA damage of peripheral blood polymorphonuclear leukocytes,selectively induced by chronic arsenic exposure,is associated with extent of arsenic-related skin lesions

There is increasing evidence that oxidative stress is an important risk factor for arsenic-related diseases. Peripheral blood leukocytes constitute an important defense against microorganisms or pathogens, while the research on the impact of chronic arsenic exposure on peripheral blood leukocytes is much more limited, especially at low level arsenic exposure. The purpose of the present study was to explore whether chronic arsenic exposure affects oxidative stress of peripheral blood leukocytes and possible linkages between oxidative stress and arsenic-induced skin lesions. 75 male inhabitants recruited from an As-endemic region of China were investigated in the present study. The classification of arsenicosis was based on the degree of skin lesions. Arsenic levels were measured in drinking water and urine by Atomic Fluorescence Spectroscopy. Urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) was tested by Enzyme-Linked Immunosorbent Assay. 8-OHdG of peripheral blood leukocytes was evaluated using immunocytochemical staining. 8-OHdG-positive reactions were only present in polymorphonuclear leukocytes (PMNs), but not in monocytes (MNs). The 8-OHdG staining of PMN cytoplasm was observed in all investigated populations, while the 8-OHdG staining of PMN nuclei was frequently found along with the elevated amounts of cell debris in individuals with skin lesion. Urinary arsenic levels were increased in the severe skin lesion group compared with the normal group. No relationship was observed between drinking water arsenic or urine 8-OHdG and the degree of skin lesions. These findings indicated that the target and persistent oxidative stress in peripheral blood PMNs may be employed as a sensitive biomarker directly to assess adverse health effects caused by chronic exposure to lower levels of arsenic.     

Regionally contaminated aquifers--toxicological relevance and remediation options (Bitterfeld case study)

Large-scale contaminated megasites like Bitterfeld in eastern Germany are characterized by a regional contamination of soil, surface water and groundwater as a result of a long and varied history of chemical production. While the contaminants in soils and sediments mostly represent a localized problem, pollutants in groundwater may spread to uncontaminated areas and endanger receptors like surface water and drinking water wells according to the site-specific hydrologic regime. From the toxicological point of view, the contaminants at the Bitterfeld megasite represent a dangerous cocktail of various harmful substances coming from a multitude of sources. Appropriate remediation techniques must be able to remedy the specific problems arising from hot spot areas within the megasite in addition to preventing a further extension of the contaminated zone towards uncontaminated compartments. Therefore, a combination of specifically designed remediation technologies based on the pump and treat-principle with in situ technologies, such as reactive walls and monitored/enhanced natural attenuation, is necessary to efficiently address the miscellaneous challenges at this megasite. In this paper, the currently known contaminant distribution, the associated problems for human health and the environment and possible remediation strategies are presented for the Bitterfeld megasite.