Arsenic-induced cell proliferation is associated with enhanced ROS generation, Erk signaling and CyclinA expression

Chowdhury, Rajdeep; Chatterjee, Raghunath; Giri, Ashok K.; Mandal, Chitra; Chaudhuri, Keya

doi:10.1016/j.toxlet.2010.07.006

Cited by 77 publications

(48 citation statements)

References 41 publications

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“…The cell cycle distribution studies pointed out that -especially in case of thio-DMA V -the cell cycle arrest strongly contributes to the observed reduction in cell number; thio-DMA V and arsenite induced cell cycle arrests have also been shown before in other cellular systems [18,35]. In general a G2/M phase arrest can indicate DNA damage, inappropriate or not fully replicated DNA, DNA hypomethylation or a dysfunction of the spindle apparatus.…”

Section: Parametermentioning

confidence: 90%

Toxicological properties of the thiolated inorganic arsenic and arsenosugar metabolite thio-dimethylarsinic acid in human bladder cells

Ebert

Leffers

Weber

et al. 2014

Journal of Trace Elements in Medicine and Biology

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Thio-dimethylarsinic acid (thio-DMA(V)) has recently been identified as human metabolite after exposure toward both the human carcinogen inorganic arsenic and arsenosugars, which are the major arsenical constituents of marine algae. This study aims to get further insight in the toxic modes of action of thio-DMA(V) in cultured human urothelial cells. Among others effects of thio-DMA(V) on eight cell death related endpoints, cell cycle distribution, genotoxicity, cellular bioavailability as well as for the first time its impact on DNA damage induced poly(ADP-ribosyl)ation were investigated and compared to effects induced by arsenite. The data indicate that thio-DMA(V) exerts its cellular toxicity in a similar or even lower concentration range, however most likely via different mechanisms, than arsenite. Most interestingly, thio-DMA(V) decreased damage-induced cellular poly(ADP-ribosyl)ation by 35,000-fold lower concentrations than arsenite. The inhibition of this essential DNA-damage induced and DNA-repair related signaling reaction might contribute to inorganic arsenic induced toxicity, at least in the bladder. Therefore, and also because thio-DMA(V) is to date by far the most toxic human metabolite identified after arsenosugar intake, thio-DMA(V) should contemporary be fully (also in vivo) toxicologically characterized, to assess risks to human health related to inorganic arsenic but especially arsenosugar dietary intake.

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Section: Parametermentioning

confidence: 90%

Toxicological properties of the thiolated inorganic arsenic and arsenosugar metabolite thio-dimethylarsinic acid in human bladder cells

Ebert

Leffers

Weber

et al. 2014

Journal of Trace Elements in Medicine and Biology

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“…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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“…The resulting activation of the E2F gene family results in the expression of target genes, including cyclin E 124,125) . Several upstream factors have been proposed to be responsible for ERK activation, including oxidative stress, the PKC signaling pathway, crosstalk with cAMP signaling, and the HGF/c-Met signaling pathway [126][127][128][129] . Accordingly, it seems likely that the activity of the HGF/c-Met pathway following renal epithelial cell injury is responsible for ERK activation in the high CTN dose group.…”

Section: Modes Of Carcinogenic Actionmentioning

confidence: 99%

Possible Carcinogenic Mechanisms Underlying Renal Carcinogens in Food

Umemura

2014

Food Safety

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Some chemicals contained in foods originating from a variety of sources including natural plants, food additives, residual pesticides, mycotoxins and by-products created during food processing and/or cooking have previously been demonstrated to be carcinogenic at various sites in rodents. This review focuses on reported renal carcinogens in natural products such as d-limonene and aristolochic acid (AA), food additives such as potassium bromate (KBrO 3 ) and madder color (MC), as well as mycotoxins such as ochratoxin A (OTA) and citrinin (CTN) and discusses data from reporter gene mutation assays. In addition to in vivo genotoxicity, recent information on several factors related to chemical carcinogenesis, such as DNA modifications and cell proliferation, gave insight into possible modes of action that underlie renal carcinogenesis. Given that neither d-limonene nor CTN induced increases in mutant frequencies (MFs) in some reporter genes, cell proliferation at target sites arising from compensatory and/or direct mitogenic action may play a key role in the carcinogenic mechanism of these compounds. Clear positive results from reporter gene mutation assays for AA, MC and OTA strongly suggest that genotoxic mechanisms are involved in carcinogenesis induced by these agents. While KBrO 3 elevated MFs in the red/gam gene (Spi − ), it did so to a lower extent than did potent genotoxic carcinogens. Accordingly, the participation of genotoxic mechanisms in KBrO 3 -induced renal carcinogenesis may be limited.

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Arsenic-induced cell proliferation is associated with enhanced ROS generation, Erk signaling and CyclinA expression

Cited by 77 publications

References 41 publications

Toxicological properties of the thiolated inorganic arsenic and arsenosugar metabolite thio-dimethylarsinic acid in human bladder cells

Toxicological properties of the thiolated inorganic arsenic and arsenosugar metabolite thio-dimethylarsinic acid in human bladder cells

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

Possible Carcinogenic Mechanisms Underlying Renal Carcinogens in Food

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