CoChat
Sign Up
Cited by 26Arsenic contamination and mitigationImmunotoxicology and immune responsesNonmelanoma Skin Cancer Studies

Aberrant immune responses in arsenical skin cancers

Open access
Lee, Chih‐Hung, Liao, Wei‐Ting, Yu, Hsin‐Su·2011·The Kaohsiung Journal of Medical Sciences
DOI 10.1016/j.kjms.2011.05.007PMC PMC11916620
Open this paper in CoChat — free accountOpen PDF

Abstract

Arsenic is a well‐known human carcinogen. It also impairs immune functions and activation in many aspects. However, only a small portion of arsenic‐exposed population develops skin abnormalities, including Bowen's disease and skin cancers. Differential immune activation among the individuals might account for the different susceptibilities. In patients with arsenic‐induced Bowen's disease, there is a selective CD4 T‐cell apoptosis through tumor necrosis factor‐alpha pathway, decrease in macrophage differentiation and phagocytosis, reduced Langerhans cell numbers and dendrites, altered regulatory T‐cell distribution, and other immune alterations. Several lines of evidence from mouse and fish studies also confirmed the potent and multifaceted effects of arsenic in the immune system. The molecular bases of immunosuppression by arsenic in lymphocytes may include chromosomal and DNA abnormalities, decreased T‐cell receptor activation, and the cellular status of oxidation and methylation. This article also reviews the causative and differential role of selective CD4 cell apoptosis and the carcinogenesis of arsenic‐induced Bowen's disease.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.kjms.2011.05.007

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The fact that arsenic-induced skin cancers do not usually occur in sun-exposed skin might result from the synergistic apoptotic effects of UV and arsenic in keratinocytes, in which combined UVB irradiation and arsenic treatment results in pro-apoptotic effects induced by activation of Caspase 8 and Caspase 9.

    “The fact that arsenic-induced skin cancers do not usually occur in sun-exposed skin might result from the synergistic apoptotic effects of UV and arsenic in keratinocytes, in which the combined use of UVB irradiation and arsenic treatment results in the pro-apoptotic effects induced by activation of Caspase 8 and Caspase 9 [44,45].”

    From Molecular Mechanisms of UV-Induced Apoptosis and Its Effects on Skin Residential Cells: The Implication in UV-Based Phototherapy (2013) · cites this paper as [44]

    Split into 2 atoms — 0 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.

    Experimental — accuracy not yet measured

  • A combined use of UVB irradiation and arsenic treatments results in anti-proliferative and pro-apoptotic effects by activation of Caspase 8 and 9 in keratinocytes.

    “A combined use of UVB irradiation and arsenic treatments has been found to result in the anti-proliferative and pro-apoptotic effects by activation of Caspase 8 and 9 in keratinocytes [44,45].”

    From Molecular Mechanisms of UV-Induced Apoptosis and Its Effects on Skin Residential Cells: The Implication in UV-Based Phototherapy (2013) · cites this paper as [44]

    The ‘Cell targets of immune system in arsenic-induced skin cancers’ section describes arsenic-related apoptosis in T cells, not keratinocytes. The ‘Selective CD4 cell apoptosis’ section discusses arsenic-treated keratinocytes but does not report their apoptosis. Searches for UVB, combined irradiation and arsenic treatment, and caspases 8 and 9 found no passage addressing the claimed effect. (LLM, conf=0.77)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

No references could be resolved yet.

Research works printed but not linked: 42

  1. Amasa SK. Arsenic pollution at Obuasi Goldmine, town, and surrounding countryside. Environ Health Perspect 1975;12: 131e5.
  2. Andres A. Cancer incidence after immunosuppressive treat- ment following kidney transplantation. Crit Rev Oncol Hema- tol 2005;56:71e85.
  3. Burns LA, Munson AE. Gallium arsenide selectively inhibits T cell proliferation and alters expression of CD25 (IL-2R/p55). J Pharmacol Exp Ther 1993;265:178e86.
  4. Yoshida T, Shimamura T, Shigeta S. Immunological effects of arsenic compounds on mouse spleen cells in vitro. Tokai J Exp Clin Med 1986;11:353e9.
  5. Sikorski EE, McCay JA, White Jr KL, Bradley SG, Munson AE. Immunotoxicity of the semiconductor gallium arsenide in female B6C3F1 mice. Fundam Appl Toxicol 1989;13:843e58.
  6. Patterson R, Vega L, Trouba K, Bortner C, Germolec D. Arsenic-induced alterations in the contact hypersensitivity response in Balb/c mice. Toxicol Appl Pharmacol 2004;198: 434e43.
  7. Waalkes MP, Liu J, Ward JM, Diwan BA. Animal models for arsenic carcinogenesis: inorganic arsenic is a transplacental carcinogen in mice. Toxicol Appl Pharmacol 2004;198:377e84.
  8. Waalkes MP, Ward JM, Liu J, Diwan BA. Transplacental carci- nogenicity of inorganic arsenic in the drinking water: induc- tion of hepatic, ovarian, pulmonary, and adrenal tumors in mice. Toxicol Appl Pharmacol 2003;186:7e17.
  9. Waalkes MP, Liu J, Germolec DR, Trempus CS, Cannon RE, Tokar EJ, et al. Arsenic exposure in utero exacerbates skin cancer response in adulthood with contemporaneous distortion of tumor stem cell dynamics. Cancer Res 2008;68:8278e85.
  10. Raqib R, Ahmed S, Sultana R, Wagatsuma Y, Mondal D, Hoque AM, et al. Effects of in utero arsenic exposure on child immunity and morbidity in rural Bangladesh. Toxicol Lett 2009;185:197e202.
  11. Nayak AS, Lage CR, Kim CH. Effects of low concentrations of arsenic on the innate immune system of the zebrafish (Danio rerio). Toxicol Sci 2007;98:118e24.
  12. Ghosh D, Bhattacharya S, Mazumder S. Perturbations in the catfish immune responses by arsenic: organ and cell specific effects. Comp Biochem Physiol C Toxicol Pharmacol 2006;143: 455e63.
  13. Lemarie A, Morzadec C, Bourdonnay E, Fardel O, Vernhet L. Human macrophages constitute targets for immunotoxic inorganic arsenic. J Immunol 2006;177:3019e27.
  14. Hernandez-Castro B, Doniz-Padilla LM, Salgado-Bustamante M, Rocha D, Ortiz-Perez MD, Jimenez-Capdeville ME, et al. Effect of arsenic on regulatory T cells. J Clin Immunol 2009;29:461e9.
  15. Andrew AS, Jewell DA, Mason RA, Whitfield ML, Moore JH, Karagas MR. Drinking-water arsenic exposure modulates gene expression in human lymphocytes from a U.S. population. Environ Health Perspect 2008;116:524e31.
  16. Wu MM, Chiou HY, Ho IC, Chen CJ, Lee TC. Gene expression of inflammatory molecules in circulating lymphocytes from arsenic-exposed human subjects. Environ Health Perspect 2003;111:1429e38.
  17. Meng Z. Effects of arsenic on DNA synthesis in human lymphocytes. Arch Environ Contam Toxicol 1993;25:525e8.
  18. Eastmond DA, Pinkel D. Detection of aneuploidy and aneu- ploidy-inducing agents in human lymphocytes using fluores- cence in situ hybridization with chromosome-specific DNA probes. Mutat Res 1990;234:303e18.
  19. Vega L, Gonsebatt ME, Ostrosky-Wegman P. Aneugenic effect of sodium arsenite on human lymphocytes in vitro: an indi- vidual susceptibility effect detected. Mutat Res 1995;334: 365e73.
  20. Hsu YH, Li SY, Chiou HY, Yeh PM, Liou JC, Hsueh YM, et al. Spontaneous and induced sister chromatid exchanges and delayed cell proliferation in peripheral lymphocytes of Bowen's disease patients and matched controls of arseniasis- hyperendemic villages in Taiwan. Mutat Res 1997;386:241e51.
  21. Wen WN, Lieu TL, Chang HJ, Wuu SW, Yau ML, Jan KY. Baseline and sodium arsenite-induced sister chromatid exchanges in cultured lymphocytes from patients with blackfoot disease and healthy persons. Hum Genet 1981;59:201e3.
  22. Lerda D. Sister-chromatid exchange (SCE) among individuals chronically exposed to arsenic in drinking water. Mutat Res 1994;312:111e20.
  23. Ghosh P, Banerjee M, De Chaudhuri S, Das JK, Sarma N, Basu A, et al. Increased chromosome aberration frequencies in the Bowen's patients compared to non-cancerous skin lesions individuals exposed to arsenic. Mutat Res 2007;632: 104e10.
  24. Menendez D, Mora G, Salazar AM, Ostrosky-Wegman P. ATM status confers sensitivity to arsenic cytotoxic effects. Muta- genesis 2001;16:443e8.
  25. Kligerman AD, Doerr CL, Tennant AH, Harrington-Brock K, Allen JW, Winkfield E, et al. Methylated trivalent arsenicals as candidate ultimate genotoxic forms of arsenic: induction of chromosomal mutations but not gene mutations. Environ Mol Mutagen 2003;42:192e205.
  26. Soto-Pena GA, Vega L. Arsenic interferes with the signaling transduction pathway of T cell receptor activation by increasing basal and induced phosphorylation of Lck and Fyn in spleen cells. Toxicol Appl Pharmacol 2008;230:216e26.
  27. Kligerman AD, Doerr CL, Tennant AH. Oxidation and methyl- ation status determine the effects of arsenic on the mitotic apparatus. Mol Cell Biochem 2005;279:113e21.
  28. Ramirez T, Garcia-Montalvo V, Wise C, Cea-Olivares R, Poirier LA, Herrera LA. S-adenosyl-L-methionine is able to reverse micronucleus formation induced by sodium arsenite and other cytoskeleton disrupting agents in cultured human cells. Mutat Res 2003;528:61e74.
  29. Tabellini G, Tazzari PL, Bortul R, Evangelisti C, Billi AM, Grafone T, et al. Phosphoinositide 3-kinase/Akt inhibition increases arsenic trioxide-induced apoptosis of acute pro- myelocytic and T-cell leukaemias. Br J Haematol 2005;130: 716e25.
  30. Zheng Y, Yamaguchi H, Tian C, Lee MW, Tang H, Wang HG, et al. Arsenic trioxide (As(2)O(3)) induces apoptosis through activation of Bax in hematopoietic cells. Oncogene 2005;24: 3339e47.
  31. El-Sabban ME, Nasr R, Dbaibo G, Hermine O, Abboushi N, Quignon F, et al. Arsenic-interferon-alpha-triggered apoptosis in HTLV-I transformed cells is associated with tax down- regulation and reversal of NF-kappa B activation. Blood 2000; 96:2849e55.
  32. Ishitsuka K, Hanada S, Uozumi K, Utsunomiya A, Arima T. Arsenic trioxide and the growth of human T-cell leukemia virus type I infected T-cell lines. Leuk Lymphoma 2000;37: 649e55.
  33. Yu HS, Chang KL, Wang CM, Yu CL. Alterations of mitogenic responses of mononuclear cells by arsenic in arsenical skin cancers. J Dermatol 1992;19:710e4.
  34. Gonsebatt ME, Vega L, Herrera LA, Montero R, Rojas E, Cebrian ME, et al. Inorganic arsenic effects on human lymphocyte stimulation and proliferation. Mutat Res 1992; 283:91e5.
  35. Yu HS, Liao WT, Chang KL, Yu CL, Chen GS. Arsenic induces tumor necrosis factor alpha release and tumor necrosis factor receptor 1 signaling in T helper cell apoptosis. J Invest Der- matol 2002;119:812e9.
  36. Yu HS, Chang KL, Yu CL, Wu CS, Chen GS, Ho JC. Defective IL-2 receptor expression in lymphocytes of patients with arsenic-induced Bowen's disease. Arch Dermatol Res 1998; 290:681e7.
  37. Vega L, Ostrosky-Wegman P, Fortoul TI, Diaz C, Madrid V, Saavedra R. Sodium arsenite reduces proliferation of human activated T-cells by inhibition of the secretion of interleukin-2. Immunopharmacol Immunotoxicol 1999;21:203e20.
  38. Soto-Pena GA, Luna AL, Acosta-Saavedra L, Conde P, Lopez- Carrillo L, Cebrian ME, et al. Assessment of lymphocyte subpopulations and cytokine secretion in children exposed to arsenic. FASEB J 2006;20:779e81.
  39. Biswas R, Ghosh P, Banerjee N, Das JK, Sau T, Banerjee A, et al. Analysis of T-cell proliferation and cytokine secretion in the individuals exposed to arsenic. Hum Exp Toxicol 2008;27:381e6.
  40. Germolec DR, Spalding J, Yu HS, Chen GS, Simeonova PP, Humble MC, et al. Arsenic enhancement of skin neoplasia by chronic stimulation of growth factors. Am J Pathol 1998;153: 1775e85.
  41. Germolec DR, Yoshida T, Gaido K, Wilmer JL, Simeonova PP, Kayama F, et al. Arsenic induces overexpression of growth factors in human keratinocytes. Toxicol Appl Pharmacol 1996; 141:308e18.
  42. Liao WT, Yu CL, Cheng-Che EL, Lee CH, Chang CS, Chang LW, et al. Differential effects of arsenic on cutaneous and systemic immunity: focusing on CD4þ cell apoptosis in patients with arsenic-induced Bowen's disease. Carcinogen- esis 2009;30:1064e72.

Cited by

Sorted by citations

Authors
Lee, C., Liao, W., & Yu, H.
Affiliations
Kaohsiung Medical University (TW)
Corresponding author
Yu, Hsin‐Su
ORCID
Venue
The Kaohsiung Journal of Medical Sciences
Publisher
Wiley
Published
2011-07-06
Volume
27
Issue
9
Pages
396-401
ISSN
  • 1607-551X (ISSN-L)
  • 2410-8650
DOI
10.1016/j.kjms.2011.05.007
PMC
PMC11916620
OpenAlex
W2051054651
Cited by
26
References
0
Citations by year
2026: 1 · 2025: 2 · 2024: 3 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 3 · 2019: 1 · 2018: 2 · 2016: 4 · 2015: 3 · 2014: 1 · 2013: 2
FWCI
0.11
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • The Kaohsiung Journal of Medical Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • National Science Council (NSC95‐2314‐B‐037‐024, NSC96‐2314‐B‐037‐043, NSC97‐2320‐B‐010‐013‐MY3)
  • Kaohsiung Medical University (KMU‐QA096005)
Topics
  • Physical Sciences › Environmental Science › Environmental Chemistry › Arsenic contamination and mitigation
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
  • Health Sciences › Medicine › Epidemiology › Nonmelanoma Skin Cancer Studies
Keywords
arsenic, Bowen's disease, immune dysfunction, immunosuppression, CD4+ T cell apoptosis, TNF-α, macrophage differentiation, Langerhans cells, regulatory T cells, T cell receptor stimulation, DNA methylation, oxidative stress, carcinogenesis, arsenic exposure
MeSH terms
Animals, Arsenic, Bowen's Disease, Humans, Skin Neoplasms, T-Lymphocytes, Arsenic Poisoning

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review