Inorganic arsenic: A non-genotoxic carcinogen.
01 Nov 2016-Journal of Environmental Sciences-china (Chinese Academy of Sciences)-Vol. 49, Iss: 11, pp 28-37
TL;DR: The data strongly supports a non-linear dose response for the effects of inorganic arsenic, and in various in vitro and in vivo models and in human epidemiology studies there appears to be a threshold for biological responses, including cancer.
Abstract: Inorganic arsenic induces a variety of toxicities including cancer. The mode of action for cancer and non-cancer effects involves the metabolic generation of trivalent arsenicals and their reaction with sulfhydryl groups within critical proteins in various cell types which leads to the biological response. In epithelial cells, the response is cell death with consequent regenerative proliferation. If this continues for a long period of time, it can result in an increased risk of cancer. Arsenicals do not react with DNA. There is evidence for indirect genotoxicity in various in vitro and in vivo systems, but these involve exposures at cytotoxic concentrations and are not the basis for cancer development. The resulting markers of genotoxicity could readily be due to the cytotoxicity rather than an effect on the DNA itself. Evidence for genotoxicity in humans has involved detection of chromosomal aberrations, sister chromatid exchanges in lymphocytes and micronucleus formation in lymphocytes, buccal mucosal cells, and exfoliated urothelial cells in the urine. Numerous difficulties have been identified in the interpretation of such results, including inadequate assessment of exposure to arsenic, measurement of micronuclei, and potential confounding factors such as tobacco exposure, folate deficiency, and others. Overall, the data strongly supports a non-linear dose response for the effects of inorganic arsenic. In various in vitro and in vivo models and in human epidemiology studies there appears to be a threshold for biological responses, including cancer.
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TL;DR: This review is based on a careful and systematic collection of the latest papers during 2010-2017 and the research results, and it illustrates the fate and ecological effects of Sb in the environment.
Abstract: Antimony (Sb) is a toxic metalloid, and its pollution has become a global environmental problem as a result of its extensive use and corresponding Sb-mining activities. The toxicity and mobility of Sb strongly depend on its chemical speciation. In this review, we summarize the current knowledge on the biogeochemical processes (including emission, distribution, speciation, redox, metabolism and toxicity) that trigger the mobilization and transformation of Sb from pollution sources to the surrounding environment. Natural phenomena such as weathering, biological activity and volcanic activity, together with anthropogenic inputs, are responsible for the emission of Sb into the environment. Sb emitted in the environment can adsorb and undergo redox reactions on organic or inorganic environmental media, thus changing its existing form and exerting toxic effects on the ecosystem. This review is based on a careful and systematic collection of the latest papers during 2010-2017 and our research results, and it illustrates the fate and ecological effects of Sb in the environment.
268 citations
TL;DR: The arsenic metabolic pathway, the roles of the methylated arsenic metabolites in toxicity and in the therapeutic efficacy for the treatments of solid tumors, APL and/or non-APL malignancies are focused on.
Abstract: // Islam Khairul 1 , Qian Qian Wang 1,2 , Yu Han Jiang 1,3 , Chao Wang 1 and Hua Naranmandura 1,2,3 1 Department of Toxicology, School of Medicine and Public Health, Zhejiang University, Hangzhou, China 2 College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China 3 Ocean College, Zhejiang University, Hangzhou, China Correspondence to: Hua Naranmandura, email: // Keywords : arsenite, acute promyelocytic leukemia Received : November 23, 2016 Accepted : January 11, 2017 Published : January 18, 2017 Abstract A variety of studies indicated that inorganic arsenic and its methylated metabolites have paradoxical effects, namely, carcinogenic and anticancer effects. Epidemiological studies have shown that long term exposure to arsenic can increase the risk of cancers of lung, skin or bladder in man, which is probably associated with the arsenic metabolism. In fact, the enzymatic conversion of inorganic arsenic by Arsenic (+3 oxidation state) methyltransferase (AS3MT) to mono- and dimethylated arsenic species has long been considered as a major route for detoxification. However, several studies have also indicated that biomethylation of inorganic arsenic, particularly the production of trivalent methylated metabolites, is a process that activates arsenic as a toxin and a carcinogen. On the other hand, arsenic trioxide (As 2 O 3 ) has recently been recognized as one of the most effective drugs for the treatment of APL. However, elaboration of the cytotoxic mechanisms of arsenic and its methylated metabolites in eradicating cancer is sorely lacking. To provide a deeper understanding of the toxicity and carcinogenicity along with them use of arsenic in chemotherapy, caution is required considering the poor understanding of its various mechanisms of exerting toxicity. Thereby, in this review, we have focused on arsenic metabolic pathway, the roles of the methylated arsenic metabolites in toxicity and in the therapeutic efficacy for the treatments of solid tumors, APL and/or non-APL malignancies.
195 citations
Cites background from "Inorganic arsenic: A non-genotoxic ..."
...The thiolated arsenicals are readily taken up by bladder cells and quickly converted to the corresponding trivalent oxygenated form of arsenic and showed their toxicities [54, 55]....
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TL;DR: Current knowledge on the mechanisms of arsenic carcinogenesis is summarized and changes to the epigenome, metabolism of arsenic and epigenetic mechanisms, and cytotoxicity and regeneration proliferation are focused on to garner a broader perspective.
153 citations
TL;DR: Dynamic monitoring of real-time cellular responses to fourteen arsenicals provided useful information for comparison of their relative cytotoxicity.
Abstract: The occurrence of a large number of diverse arsenic species in the environment and in biological systems makes it important to compare their relative toxicity. The toxicity of arsenic species has been examined in various cell lines using different assays, making comparison difficult. We report real-time cell sensing of two human cell lines to examine the cytotoxicity of fourteen arsenic species: arsenite (AsIII), monomethylarsonous acid (MMAIII) originating from the oxide and iodide forms, dimethylarsinous acid (DMAIII), dimethylarsinic glutathione (DMAGIII), phenylarsine oxide (PAOIII), arsenate (AsV), monomethylarsonic acid (MMAV), dimethylarsinic acid (DMAV), monomethyltrithioarsonate (MMTTAV), dimethylmonothioarsinate (DMMTAV), dimethyldithioarsinate (DMDTAV), 3-nitro-4-hydroxyphenylarsonic acid (Roxarsone, Rox), and 4-aminobenzenearsenic acid (p-arsanilic acid, p-ASA). Cellular responses were measured in real time for 72hr in human lung (A549) and bladder (T24) cells. IC50 values for the arsenicals were determined continuously over the exposure time, giving rise to IC50 histograms and unique cell response profiles. Arsenic accumulation and speciation were analyzed using inductively coupled plasma-mass spectrometry (ICP-MS). On the basis of the 24-hr IC50 values, the relative cytotoxicity of the tested arsenicals was in the following decreasing order: PAOIII≫MMAIII≥DMAIII≥DMAGIII≈DMMTAV≥AsIII≫MMTTAV>AsV>DMDTAV>DMAV>MMAV≥Rox≥p-ASA. Stepwise shapes of cell response profiles for DMAIII, DMAGIII, and DMMTAV coincided with the conversion of these arsenicals to the less toxic pentavalent DMAV. Dynamic monitoring of real-time cellular responses to fourteen arsenicals provided useful information for comparison of their relative cytotoxicity.
118 citations
TL;DR: A review of sample preparation, separation, detection, and method validation for arsenic speciation analysis can be found in this article, where an emphasis is placed on chromatographic separation techniques, relating the physicochemical properties of arsenic species to their efficient separation.
Abstract: More than 100 different arsenic species of diverse characteristics are present in the environment and biological systems. The identification and quantification of individual arsenic species are critical to understanding the distribution, environmental fate and behaviour, metabolism, and toxicity of arsenic. This review summarizes sample preparation, separation, detection, and method validation for arsenic speciation analysis. An emphasis is placed on chromatographic separation techniques, relating the physicochemical properties of arsenic species to their efficient separation. Anion exchange, cation exchange, reversed-phase, ion pair, and size exclusion chromatography are useful to separate various arsenic species. Recent research has explored hydrophilic interaction liquid chromatography (HILIC), multiple separation mechanisms, and testing of fluorophenyl and graphene oxide stationary phases for the separation of arsenic species. Sample preparation, extraction of arsenic species, recovery of arsenic species from separation columns, and method validation are discussed in light of their importance to the integrity and accuracy of speciation analysis.
80 citations
References
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01 Jan 2009
TL;DR: Arsenic in drinking water: not just a problem for Bangladesh D. van Halem, S. A. Bakker, G. L. Amy, and J. C. van Dijk Delft University of Technology.
Abstract: Arsenic in drinking water: not just a problem for Bangladesh D. van Halem, S. A. Bakker, G. L. Amy, and J. C. van Dijk Delft University of Technology, Faculty of Civil Engineering and Geosciences, Stevinweg 1, 2628 CN Delft, The Netherlands UNESCO-IHE, Westvest 7, 2611 AX Delft, The Netherlands Received: 11 December 2008 – Accepted: 15 February 2009 – Published: 26 February 2009 Correspondence to: D. van Halem (d.vanhalem@tudelft.nl) Published by Copernicus Publications on behalf of the Delft University of Technology.
1,696 citations
TL;DR: The theory that human cancer is the end-result of several successive cellular changes is tested by examining the age specific mortality rates for 17 types of cancer and provides a possible explanation for the observation that circumcision exerts an important protective effect against the development of cancer of the penis only if it be carried out early in life.
Abstract: The theory that human cancer is the end-result of several successive cellular changes is tested by examining the age specific mortality rates for 17 types of cancer. On the supposition that the carcinogenic factors responsible have remained approximately constant over the past 75 years, the rates for cancer of the oesophagus, stomach, colon, rectum and pancreas in men and for cancer of the stomach, colon, rectum and pancreas in women accord, in general, with the theory.
The mortality rates for cancer of the lung, bladder and prostate in men and for cancer of the lung, breast, ovary and cervix and corpus uteri in women also accord with the theory, if it is postulated that the carcinogenic factors responsible have varied in strength.
A formula has been obtained which can be used to weight the strengths of the carcinogenic factors at different periods and it is shown that the time when the strength of the factors responsible for the individual changes is of greatest importance varies according to which change in the series is affected. The conclusion provides a possible explanation for the observation that circumcision exerts an important protective effect against the development of cancer of the penis only if it be carried out early in life.
1,323 citations
TL;DR: A biologically based, computerized description of carcinogenesis was used to show that the increase in cell proliferation can account for the carcinogenicity of nongenotoxic compounds.
Abstract: Chemicals that induce cancer at high doses in animal bioassays often fail to fit the traditional characterization of genotoxins. Many of these nongenotoxic compounds (such as sodium saccharin) have in common the property that they increase cell proliferation in the target organ. A biologically based, computerized description of carcinogenesis was used to show that the increase in cell proliferation can account for the carcinogenicity of nongenotoxic compounds. The carcinogenic dose-response relationship for genotoxic chemicals (such as 2-acetylaminofluorene) was also due in part to increased cell proliferation. Mechanistic information is required for determination of the existence of a threshold for the proliferative (and carcinogenic) response of nongenotoxic chemicals and the estimation of risk for human exposure.
1,040 citations
"Inorganic arsenic: A non-genotoxic ..." refers background in this paper
...Although known for many decades, it is also now wellaccepted that cancers arise from pluripotential cells in tissues, that are commonly referred to as tissue stem cells (Armitage and Doll, 1954; Moolgavkar and Knudson, 1981; Greenfield et al., 1984; Cohen and Ellwein, 1990; Cohen and Arnold, 2011)....
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TL;DR: A model for carcinogenesis is presented that provides a framework for understanding the roles of "spontaneous" events, hereditary factors, and environmental agents in human carcinogenesis and for interpreting experimental carcinogenesis.
Abstract: A model for carcinogenesis is presented that provides a framework for understanding the roles of "spontaneous" events, hereditary factors, and environmental agents in human carcinogenesis and for interpreting experimental carcinogenesis. This model incorporates two features: a) transition of target stem cells into cancer cells via an intermediate stage in two irreversible steps, and b) growth and differentiation of normal target and intermediate cells. Cast in mathematical terms, the model can be fitted to age-specific incidence data on human cancers of both children and adults and can illuminate the relative importance of agents that affect transition rates, tissue growth, and tissue differentiation. This is illustrated by application of the model to a) the epidemiology of lung cancer with emphasis on the role of cigarette smoking and b) the epidemiology of breast cancer with emphasis on the roles of hormones, radiation, and hereditary. The nature of the two events and of the intermediate stage is considered in light of hereditary conditions that predispose to cancer in humans. The modes of action of radiation and chemicals in carcinogenesis are discussed, as are predictions based on the model and amenable to experimental verification.
1,032 citations
"Inorganic arsenic: A non-genotoxic ..." refers background in this paper
...During the past two decades, there have been a number of publications examining micronucleus formation in one of the target tissues in arsenic carcinogenesis, the urothelium (Basu et al., 2001, 2002, 2004; Ghosh et al., 2006, 2007, 2008; Moore et al., 1997; Paul et al., 2013)....
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...Case–control study of arsenic in drinking water and kidney cancer in uniquely exposed northern Chile....
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...However, exposure to inorganic arsenic in the drinking water in some parts of the world remains at extremely high levels, such as in Taiwan, China, Bangladesh, India, Chile, Argentina, and Mexico (IARC, 2012; Cohen et al., 2013)....
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...Most of these studies have been performed in populations in West Bengal (Basu et al., 2001, 2002, 2004; Ghosh et al., 2006, 2007, 2008; Mahata et al., 2004; Paul et al., 2013), but occasionally in other populations as well, such as in Chile (Moore et al., 1997)....
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891 citations