PubMed · 13080190
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G A JOHNSON. 1953. An arsine problem: engineering notes.. https://doi.org/10.1080/00968205309343934
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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.
Concentrations of As, Al and some heavy metals (V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Cd, Pb) were measured in drinking waters from Siena and Grosseto districts, South Tuscany, Italy. The analysis, performed mostly by electrothermal activated atomic absorption spectroscopy equipped with graphite furnace, and in some cases high-resolution inductively coupled plasma mass spectrometry, indicated that concentrations of the elements were generally far below the maximum allowed concentration (MAC). However, the concentration of As in some of the waters at sources or at the terminals of the water webs was relatively high (largest value, 14.4(2) microg/l) when compared to the MAC(As) value (10 microg/l, December 25, 2003; Italian Law). Relatively high concentrations of some metals had been detected in a few samples from the ends of the distribution webs, when compared to values at sources. These effects are probably due to leaching from metal pipes. A general 'metal index' (MI) for drinking water, which takes into account possible additive effects of N heavy metals on the human health that helps to quickly evaluate the overall quality of drinking waters, is introduced in this paper as MI=?(i=1,N)[C(i)/(MAC)(i)]. Samples from Ermicciolo spring and Siena water web had MI values of 1.1 and 1.3, respectively, showing that the quality of drinking water in town is somewhat worse than that at one of the main sources, at least regarding the 12 elements taken into account.
For the first time, biological tissues (hair, nails, and skin-scales) of arsenic victims from an arsenic affected area of West Bengal (WB), India were analyzed for trace elements. Analysis was carried out by inductively coupled plasma-mass spectrometry (ICP-MS) for 10 elements (As, Se, Hg, Zn, Pb, Ni, Cd, Mn, Cu, and Fe). A microwave digester was used for digestion of the tissue samples. To validate the method, certified reference materials--human hair (GBW 07601) and bovine muscle (CRM 8414)--were analyzed for all elements. The W test was used to study the normal/log normal distribution for each element in the tissue samples. For hair (n=44) and nails (n=33), all elements show log-normal distribution. For skin-scale samples (n=11), data are not sufficient to provide the information about the trend. Geometric mean, standard error, and range for each element were presented and compared with literature values for other populations. This study reveals the higher levels of toxic elements As, Mn, Pb, and Ni in the tissue samples compared with available values in the literature. The elevated levels of these toxic metals in the tissues may be due to exposure of these elements through drinking water and food. The correlations of Mn and Ni with other essential elements, e.g. Fe, Cu, Zn, suggest that Mn and Ni may substitute for those elements in hair, nails, and skin-scales. However, correlation represents the relation between two elements only and does not take into consideration of the presence of other elements. Principle component analysis was applied to explain the behavior among the elements present in hair and nails. This study reveals that in the arsenic-affected areas of WB, the concentrations of other toxic elements in drinking water and foodstuff should be monitored to evaluate the arsenic poisoning.