Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells

Stueckle, Todd A.; Lu, Yongju; Davis, Mary Ellen; Wang, Liying; Jiang, Bing-Hua; Holásková, Ida; Schafer, Rosana; Barnett, John B.; Rojanasakul, Yon

doi:10.1016/j.taap.2012.04.003

Cited by 76 publications

(65 citation statements)

References 58 publications

(110 reference statements)

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“…iAs-Chronic low-dose exposure to iAs is known to cause cells to undergo EMT (42,53,54). As cells go through EMT, changes in cell morphology and expression patterns of EMT markers occur.…”

Section: Transformation Of Cells By Low-dose Chronic Exposure Tomentioning

confidence: 99%

Quantitative Mass Spectrometry Reveals Changes in Histone H2B Variants as Cells Undergo Inorganic Arsenic-Mediated Cellular Transformation

Rea

Eleazer

Eckstein

et al. 2016

Molecular & Cellular Proteomics

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Exposure to inorganic arsenic, a ubiquitous environmental toxic metalloid, leads to carcinogenesis. However, the mechanism is unknown. Several studies have shown that inorganic arsenic exposure alters specific gene expression patterns, possibly through alterations in chromatin structure. While most studies on understanding the mechanism of chromatin-mediated gene regulation have focused on histone post-translational modifications, the role of histone variants remains largely unknown. Incorporation of histone variants alters the functional properties of chromatin. To understand the global dynamics of chromatin structure and function in arsenic-mediated carcinogenesis, analysis of the histone variants incorporated into the nucleosome and their covalent modifications is required. Here we report the first global mass spectrometric analysis of histone H2B variants as cells undergo arsenic-mediated epithelial to mesenchymal transition. We used electron capture dissociation-based top-down tandem mass spectrometry analysis validated with quantitative reverse transcription real-time polymerase chain reaction to identify changes in the expression levels of H2B variants in inorganic arsenic-mediated epithelial-mesenchymal transition. We identified changes in the expression levels of specific histone H2B variants in two cell types, which are dependent on dose and length of exposure of inorganic arsenic. In particular, we found increases in H2B variants H2B1H/1K/1C/1J/1O and H2B2E/2F, and significant decreases in H2B1N/1D/1B as cells undergo inorganic arsenic-mediated epithelial-mesenchymal transition. The analysis of these histone vari-

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“…iAs-Chronic low-dose exposure to iAs is known to cause cells to undergo EMT (42,53,54). As cells go through EMT, changes in cell morphology and expression patterns of EMT markers occur.…”

Section: Transformation Of Cells By Low-dose Chronic Exposure Tomentioning

confidence: 99%

Quantitative Mass Spectrometry Reveals Changes in Histone H2B Variants as Cells Undergo Inorganic Arsenic-Mediated Cellular Transformation

Rea

Eleazer

Eckstein

et al. 2016

Molecular & Cellular Proteomics

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“…Exposure to a carcinogenic metal, such as arsenic, has been associated with altered gene expression patterns both in vitro and in vivo, and it has been demonstrated that the arsenicinduced changes in gene expression may be epigenetically regulated (2)(3)(4)(5)(6)(7)(8)(9). Although arsenic is capable of inducing changes in gene expression by altering the levels of post-translational histone modifications in the promoters of genes, alterations in the expression of the histone genes themselves by arsenic has not been studied.…”

mentioning

confidence: 99%

Arsenic Induces Polyadenylation of Canonical Histone mRNA by Down-regulating Stem-Loop-binding Protein Gene Expression

Brocato

Fang

Chervona

et al. 2014

Journal of Biological Chemistry

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“…ROS production has also been linked with gene expression changes in HBE cells consistent with several of the proposed mechanisms for arsenic carcinogenesis [144] including oxidative stress, DNA damage and a weakened tumor-suppression response [165,168,195]. Suckle et al [195] assessed the malignant potential of in vitro arsenic-transformed cells by injecting them into mice.…”

Section: Studies Show That Hbe and Hpf Cells Generate Elevated Ros Lementioning

confidence: 92%

“…Enhanced arsenic-induced ROS generation and accumulation have been associated with dose-dependent responses in rates of cell proliferation and colony formation in HBE cells [193][194][195][196] as well as anti-apoptotic signaling [195]. Increased cell proliferation is a distinguishing characteristic of cancer cells and is crucial for tumor formation, while apoptosis plays an important role in killing abnormal cells so that they cannot form tumors [193].…”

Section: Studies Show That Hbe and Hpf Cells Generate Elevated Ros Lementioning

confidence: 99%

Health Effects Associated with Inhalation of Airborne Arsenic Arising from Mining Operations

et al. 2014

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Arsenic in dust and aerosol generated by mining, mineral processing and metallurgical extraction industries, is a serious threat to human populations throughout the world. Major sources of contamination include smelting operations, coal combustion, hard rock mining, as well as their associated waste products, including fly ash, mine wastes and tailings. The number of uncontained arsenic-rich mine waste sites throughout the world is of growing concern, as is the number of people at risk of exposure. Inhalation exposures to arsenic-bearing dusts and aerosol, in both occupational and environmental settings, have been definitively linked to increased systemic uptake, as well as carcinogenic and non-carcinogenic health outcomes. It is therefore becoming increasingly important to identify human populations and sensitive sub-populations at risk of exposure, and to better understand the modes of action for pulmonary arsenic toxicity and carcinogenesis. In this paper we explore the contribution of smelting, coal combustion, hard rock mining and their associated waste products to atmospheric arsenic. We also report on the current understanding of the health effects of inhaled arsenic, citing results from various toxicological, biomedical and epidemiological studies. This review is particularly aimed at OPEN ACCESSGeosciences 2014, 4 129 those researchers engaged in the distinct, but complementary areas of arsenic research within the multidisciplinary field of medical geology.Arsenic is the 20th most abundant element in the earth's crust and may be released into the atmosphere as a result of natural processes and anthropogenic activities [1]. Environmental arsenic is released via chemical and physical weathering processes, biological activity and volcanic emissions, while anthropogenic sources include mining, metal smelting and burning of coal. Annual global arsenic emissions are estimated to be 24,000 t [2], with around 60% originating from copper smelting and coal combustion alone [3]. In some urban and highly industrialized areas, less than 2% of the atmospheric arsenic inputs originate from natural sources [3].Emissions of arsenic-bearing particulate matter (PM) are of particular concern for human populations living in proximity to an emission source. Arsenic and inorganic arsenic compounds are classified as Group 1 carcinogens and are associated with cancers of the lung, bladder, kidney, skin, liver and prostate [2]. It should be noted that within the general population, inhalation is only considered a minor exposure pathway for inorganic arsenic compounds, and ingestion is considered the primary exposure pathway [2]. However, populations living in the vicinity of an arsenic emission source have an increased risk of additional exposure through inhalation of arsenic-contaminated particulates [4][5][6][7][8][9].Despite their substantial contribution to global atmospheric arsenic species, mining operations play an understudied role in the generation of contaminated dust and aerosols [10]. To identify some of the emerging ...

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Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells

Cited by 76 publications

References 58 publications

Quantitative Mass Spectrometry Reveals Changes in Histone H2B Variants as Cells Undergo Inorganic Arsenic-Mediated Cellular Transformation

Quantitative Mass Spectrometry Reveals Changes in Histone H2B Variants as Cells Undergo Inorganic Arsenic-Mediated Cellular Transformation

Arsenic Induces Polyadenylation of Canonical Histone mRNA by Down-regulating Stem-Loop-binding Protein Gene Expression

Health Effects Associated with Inhalation of Airborne Arsenic Arising from Mining Operations

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