Mechanisms and Immune Dysregulation in Arsenic Skin Carcinogenesis

Lee, Chih‐Hung; Liao, Wei‐Ting; Yu, Hsin‐Su

doi:10.4236/jct.2010.12013

Cited by 5 publications

(2 citation statements)

References 122 publications

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“…The ability of As(III) to induce transformations in various types of human cells has been studied in vitro (Chen & Costa, ), but there is no research on intestinal cells. Studies indicate that As carcinogenesis might result from oxidative stress, altered growth factors, chromosomal abnormality, immune dysregulation and aberrant epigenetic regulations (Lee, Liao, & Yu, ). The aim of the present study is to determine whether chronic exposure to As(III) favors the appearance of characteristics typical of transformed cells in intestinal epithelial cells.…”

Section: Introductionmentioning

confidence: 99%

Effect of chronic exposure to inorganic arsenic on intestinal cells

Chiocchetti

Vélez

Devesa

2019

J of Applied Toxicology

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Chronic exposure to inorganic arsenic (As)—As(III) + As(V)—is associated with type 2 diabetes, vascular diseases and various types of cancer. Although the oral route is the main way of exposure to inorganic As, the adverse gastrointestinal effects produced by chronic exposure are not well documented. The aim of the present study is to evaluate the effect of chronic exposure to As(III) on the intestinal epithelium. For this purpose, NCM460 cells, non‐transformed epithelial cells from the human colon, were exposed to As(III) (0.01‐0.2 mg/L) for 6 months and monitored for acquisition of a tumor‐like phenotype. Secretion of matrix metalloproteinases, histone modifications (H3 acetylation), hyperproliferation capacity, formation of floating spheres, anchorage‐independent growth, release of cytokine interleukin‐8 and expression of relevant genes in colon tumorigenesis were assessed. The results show a maintained proinflammatory response from the beginning, with an increase in interleukin‐8 secretion (≤570%). Downregulation of CDX1 and CDX2 was also observed. After 14 weeks of exposure, cells presented marked increases in matrix metalloproteinase‐2 secretion and histone modifications. As(III)‐treated cells were hyperproliferative, grew in low‐serum media and were able to form free‐floating spheres. Overall, these data suggest that exposure of human colon epithelial cells to As(III) facilitates acquisition of transformed cell characteristics.

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Section: Introductionmentioning

confidence: 99%

Effect of chronic exposure to inorganic arsenic on intestinal cells

Chiocchetti

Vélez

Devesa

2019

J of Applied Toxicology

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“…To reduce the risk of arsenic-induced adverse health effects, understanding the pathophysiology of arsenical skin cancers may help develop clinic treatments to halt the chronological march of the arsenic cancers. The molecular mechanisms of arsenic carcinogenesis still remain unclear, although aberrant cell proliferation, increased oxidative stresses, chromosome abnormalities and immune dysregulation might be involved [ 5 , 6 , 7 , 8 ]. Aberrant cell proliferation followed by uncontrolled growth are the critical events in the initiation of carcinogenesis.…”

Section: Introductionmentioning

confidence: 99%

Arsenite Regulates Prolongation of Glycan Residues of Membrane Glycoprotein: A Pivotal Study via Wax Physisorption Kinetics and FTIR Imaging

Lee

Hsu

Huang

et al. 2016

IJMS

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Arsenic exposure results in several human cancers, including those of the skin, lung, and bladder. As skin cancers are the most common form, epidermal keratinocytes (KC) are the main target of arsenic exposure. The mechanisms by which arsenic induces carcinogenesis remains unclear, but aberrant cell proliferation and dysregulated energy homeostasis play a significant role. Protein glycosylation is involved in many key physiological processes, including cell proliferation and differentiation. To evaluate whether arsenite exposure affected protein glycosylation, the alteration of chain length of glycan residues in arsenite treated skin cells was estimated. Herein we demonstrated that the protein glycosylation was adenosine triphosphate (ATP)-dependent and regulated by arsenite exposure by using Fourier transform infrared (FTIR) reflectance spectroscopy, synchrotron-radiation-based FTIR (SR-FTIR) microspectroscopy, and wax physisorption kinetics coupled with focal-plane-array-based FTIR (WPK-FPA-FTIR) imaging. We were able to estimate the relative length of surface protein-linked glycan residues on arsenite-treated skin cells, including primary KC and two skin cancer cell lines, HSC-1 and HaCaT cells. Differential physisorption of wax adsorbents adhered to long-chain (elongated type) and short-chain (regular type) glycan residues of glycoprotein of skin cell samples treated with various concentration of arsenite was measured. The physisorption ratio of beeswax remain/n-pentacosane remain for KC cells was increased during arsenite exposure. Interestingly, this increase was reversed after oligomycin (an ATP synthase inhibitor) pretreatment, suggesting the chain length of protein-linked glycan residues is likely ATP-dependent. This is the first study to demonstrate the elongation and termination of surface protein-linked glycan residues using WPK-FPA-FTIR imaging in eukaryotes. Herein the result may provide a scientific basis to target surface protein-linked glycan residues in the process of arsenic carcinogenesis.

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Cell cycle pathway dysregulation in human keratinocytes during chronic exposure to low arsenite

Al-Eryani

Waigel

Jala

et al. 2017

Toxicology and Applied Pharmacology

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Background Arsenic is naturally prevalent in the earth’s crust and widely distributed in air and water. Chronic low arsenic exposure is associated with several cancers in vivo, including skin cancer, and with transformation in vitro of cell lines including immortalized human keratinocytes (HaCaT). Arsenic also is associated with cell cycle dysregulation at different exposure levels in multiple cell lines. In this work, we analyzed gene expression in HaCaT cells to gain an understanding of gene expression changes contributing to transformation at an early time point. Methods HaCaT cells were exposed to 0 or 100 nM NaAsO2 for 7 weeks. Total RNA was purified and analyzed by microarray hybridization. Differential expression with fold change ≥|1.5| and p-value ≤0.05 was determined using Partek Genomic Suite™ and pathway and network analyses using MetaCore™ software (FDR ≤0.05). Cell cycle analysis was performed using flow cytometry. Results 644 mRNAs were differentially expressed. Cell cycle/cell cycle regulation pathways predominated in the list of dysregulated pathways. Genes involved in replication origin licensing were enriched in the network. Cell cycle assay analysis showed an increase in G2/M compartment in arsenite-exposed cells. Conclusions Arsenite exposure induced differential gene expression indicating dysregulation of cell cycle control, which was confirmed by cell cycle analysis. The results suggest that cell cycle dysregulation is an early event in transformation manifested in cells unable to transit G2/M efficiently. Further study at later time points will reveal additional changes in gene expression related to transformation processes.

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Mechanisms and Immune Dysregulation in Arsenic Skin Carcinogenesis

Cited by 5 publications

References 122 publications

Effect of chronic exposure to inorganic arsenic on intestinal cells

Effect of chronic exposure to inorganic arsenic on intestinal cells

Arsenite Regulates Prolongation of Glycan Residues of Membrane Glycoprotein: A Pivotal Study via Wax Physisorption Kinetics and FTIR Imaging

Cell cycle pathway dysregulation in human keratinocytes during chronic exposure to low arsenite

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