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Developing a good solution for arsenic.

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K S Betts. 2001-10-01. Developing a good solution for arsenic.. https://doi.org/10.1021/es0125117

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Deficient arsenic methylation and global proteomic reprogramming in human keratinocytes during arsenic-induced skin carcinogenesis.

Chronic inorganic arsenic (iAs) exposure affects > 220 million people worldwide and skin cancer is a hallmark of long-term iAs exposure. Limited information exists regarding arsenic methylation by human keratinocytes and how methylation influences skin carcinogenesis. Inorganic arsenite (iAsIII) and its methylated metabolites disrupt diverse zinc finger proteins, leading to differential toxicity patterns. We examined arsenic methylation capacity in non-malignant human keratinocytes and interrogated proteomic remodeling across three stages of iAsIII induced malignant transformation using the well-established preclinical HaCaT model. Arsenic methylation was assessed by hydride generation cryotrapping inductively coupled-mass spectrometry and global proteomic changes were analyzed by tandem-mass tagging liquid chromatography-tandem mass spectrometry. Primary, hTERT-immortalized and HaCaT human keratinocytes exhibited negligible arsenic methylation, with iAsIII comprising at least 98.5% of total intracellular arsenic, attributable to minimal expression of arsenite methyltransferase. Proteomic profiling identified over 275 differentially expressed proteins at each stage of transformation, including multiple zinc finger proteins implicated in cell cycle control, RNA metabolism, and genome stability. Ingenuity® Pathway Analysis revealed progressive, coordinated disruption of cancer-associated pathways and regulatory networks over the transformation timeline, including zinc-coordinating upstream regulators that may explain widespread pathway dysregulation. Collectively, our findings suggest that iAsIII promotes skin carcinogenesis by disrupting C3H1- and C4-type zinc finger protein-centered regulatory networks that coordinate cancer-associated signaling and metabolic pathways in human keratinocytes, highlighting key candidates for future mechanistic studies.

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Arsenic and heavy metal contamination of vegetables grown in Samta village, Bangladesh.

Drinking of arsenic (As) contaminated well water has become a serious threat to the health of many millions in Bangladesh. However, the implications of contamination of agricultural soils from long-term irrigation with As-contaminated groundwater for phyto-accumulation in food crops, and thence dietary exposure to As, and other metals, has not been assessed previously in Bangladesh. Various vegetables were sampled in Samta village in the Jessore district of Bangladesh, and screened for As, Cd, Pb, Cu and Zn by inductively coupled plasma emission spectrometry (ICP-AES) and inductively coupled plasma mass spectrometry (ICP-MS). These local food products are the basis of human nutrition in this region and of great relevance to human health. The results revealed that the individual vegetables containing the highest mean As concentrations microg x g(-1)) are snake gourd (0.489), ghotkol (0.446), taro (0.440), green papaya (0.389), elephant foot (0.338) and Bottle ground leaf (0.306), respectively. The As concentration in fleshy vegetable material is low. In general, the data show the potential for some vegetables to accumulate heavy metals with concentrations of Pb greater than Cd. Some vegetables such as bottle ground leaf, ghotkol, taro, eddoe and elephant foot had much higher concentrations of Pb. Other leafy and root vegetables, contained higher concentrations of Zn and Cu. Bioconcentration factors (BCF) values, based on dry weight, were below 1 for all metals. In most cases, BCF values decreased with increasing metal concentrations in the soil. From the heavily As-contaminated village in Samta, BCF values for As in ladies finger, potato, ash gourd, brinjal, green papaya, ghotkol and snake gourd were 0.001, 0.006, 0.006, 0.014, 0.030, 0.034 and 0.038, respectively. Considering the average daily intake of fresh vegetables per person per day is only 130 g, all the vegetables grown at Samta had Pb concentrations that would be a health hazard for human consumption. Although the total As in the vegetables was less than the recommended maximum intake of As, it still provides a significant additional source of As in the diet.

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