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Environmental Health and Preventive Medicine
Published in: Environmental Health and Preventive Medicine 1/2021

01-12-2021 | Lung Cancer | Review article

Paradoxical effects of arsenic in the lungs

Authors: Caixia Ren, Yang Zhou, Wenwen Liu, Qi Wang

Published in: Environmental Health and Preventive Medicine | Issue 1/2021

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Abstract

High levels (> 100 ug/L) of arsenic are known to cause lung cancer; however, whether low (≤ 10 ug/L) and medium (10 to 100 ug/L) doses of arsenic will cause lung cancer or other lung diseases, and whether arsenic has dose-dependent or threshold effects, remains unknown. Summarizing the results of previous studies, we infer that low- and medium-concentration arsenic cause lung diseases in a dose-dependent manner. Arsenic trioxide (ATO) is recognized as a chemotherapeutic drug for acute promyelocytic leukemia (APL), also having a significant effect on lung cancer. The anti-lung cancer mechanisms of ATO include inhibition of proliferation, promotion of apoptosis, anti-angiogenesis, and inhibition of tumor metastasis. In this review, we summarized the role of arsenic in lung disease from both pathogenic and therapeutic perspectives. Understanding the paradoxical effects of arsenic in the lungs may provide some ideas for further research on the occurrence and treatment of lung diseases.
Literature
1.
Schuhmacher-Wolz U, Dieter HH, Klein D, Schneider K. Oral exposure to inorganic arsenic: evaluation of its carcinogenic and non-carcinogenic effects. Crit Rev Toxicol. 2009;39(4):271–98.PubMedCrossRef
2.
Chiu HF, Ho SC, Yang CY. Lung cancer mortality reduction after installation of tap-water supply system in an arseniasis-endemic area in southwestern Taiwan. Lung Cancer. 2004;46(3):265–70.PubMedCrossRef
3.
4.
Chen CJ, Chuang YC, Lin TM, Wu HY. Malignant neoplasms among residents of a Blackfoot disease-endemic area in Taiwan: high-arsenic artesian well water and cancers. Cancer Res. 1985;45(11 Pt 2):5895–9.PubMed
5.
6.
D'Ippoliti D, Santelli E, De Sario M, Scortichini M, Davoli M, Michelozzi P. Arsenic in drinking water and mortality for cancer and chronic diseases in Central Italy, 1990-2010. PLoS One. 2015;10(9):e0138182.PubMedPubMedCentralCrossRef
7.
Ferreccio C, González C, Milosavjlevic V, Marshall G, Sancha AM, Smith AH. Lung cancer and arsenic concentrations in drinking water in Chile. Epidemiology. 2000;11(6):673–9.PubMedCrossRef
8.
9.
10.
11.
12.
Ferdosi H, Dissen EK, Afari-Dwamena NA, Li J, Chen R, Feinleib M, et al. Arsenic in drinking water and lung cancer mortality in the United States: An analysis based on US counties and 30 years of observation (1950-1979). J Environ Public Health. 2016;2016:1602929.PubMedPubMedCentralCrossRef
13.
14.
Bhattacharyya P, Sen P, Ghosh A, Saha C, Bhattacharya PP, Das A, et al. Chronic lung disease and detection of pulmonary artery dilatation in high resolution computerized tomography of chest in chronic arsenic exposure. J Environ Sci Health A Tox Hazard Subst Environ Eng. 2014;49(13):1453–61.PubMedCrossRef
15.
Siddique AE, Rahman M, Hossain MI, Karim Y, Hasibuzzaman MM, Biswas S, et al. Association between chronic arsenic exposure and the characteristic features of asthma. Chemosphere. 2020;246:125790.PubMedCrossRef
16.
Yang MH, Chang KJ, Li B, Chen WS. Arsenic trioxide suppresses tumor growth through Antiangiogenesis via Notch signaling blockade in small-cell lung cancer. Biomed Res Int. 2019;2019:4647252.PubMedPubMedCentral
17.
18.
Platzbecker U, Avvisati G, Cicconi L, Thiede C, Paoloni F, Vignetti M, Ferrara F, Divona M, Albano F, Efficace F, et al. Improved outcomes with retinoic acid and arsenic trioxide compared with retinoic acid and chemotherapy in non-high-risk acute Promyelocytic leukemia: final results of the randomized Italian-German APL0406 trial. J Clin Oncol. 2017;35(6):605–612. https://​doi.​org/​10.​1200/​JCO.​2016.​67.​1982.
19.
20.
21.
22.
23.
24.
Celik I, Gallicchio L, Boyd K, Lam TK, Matanoski G, Tao X, et al. Arsenic in drinking water and lung cancer: a systematic review. Environ Res. 2008;108(1):48–55.PubMedCrossRef
25.
Chen C, Hsu L, Chiou H, Hsueh Y, Chen S, Wu M, et al. Ingested arsenic, cigarette smoking, and lung cancer risk: a follow-up study in arseniasis-endemic areas in Taiwan. JAMA. 2004;292(24):2984–90.PubMedCrossRef
26.
27.
Krug H. A study on arsenic lung cancer. Z Gesamte Inn Med. 1959;14(9):426–31.PubMed
28.
Satterlee HS. The arsenic-poisoning epidemic of 1900. Its relation to lung cancer in 1960 - an exercise in retrospective epidemiology. N Engl J Med. 1960;263:676–84.PubMedCrossRef
29.
Galy P, Touraine R, Brune J, Roudier P, Gallois P. Pulmonary cancer of arsenical origin in Beaujolais vineyeard workers. J Fr Med Chir Thorac. 1963;17:303–11.PubMed
30.
Pinto SS, Nelson KW. Arsenic toxicology and industrial exposure. Annu Rev Pharmacol Toxicol. 1976;16:95–100.PubMedCrossRef
31.
32.
Marshall G, Ferreccio C, Yuan Y, Bates M, Steinmaus C, Selvin S, et al. Fifty-year study of lung and bladder cancer mortality in Chile related to arsenic in drinking water. J Natl Cancer Inst. 2007;99(12):920–8.PubMedCrossRef
33.
Chiou H, Hsueh Y, Liaw K, Horng S, Chiang M, Pu Y, et al. Incidence of internal cancers and ingested inorganic arsenic: a seven-year follow-up study in Taiwan. Cancer Res. 1995;55(6):1296–300.PubMed
34.
35.
Cheng P, Weng S, Chiang C, Lai F. Relationship between arsenic-containing drinking water and skin cancers in the arseniasis endemic areas in Taiwan. J Dermatol. 2016;43(2):181–6.PubMedCrossRef
36.
37.
García-Esquinas E, Pollán M, Umans JG, Francesconi KA, Goessler W, Guallar E, et al. Arsenic exposure and cancer mortality in a US-based prospective cohort: the strong heart study. Cancer Epidemiol Biomark Prev. 2013;22(11):1944–53.CrossRef
38.
Zhang H, Wang L, Wang Y, Chang S. Using disability-adjusted life years to estimate the cancer risks of low-level arsenic in drinking water. J Environ Sci Health A Tox Hazard Subst Environ Eng. 2020;55(1):63–70.PubMedCrossRef
39.
Steinmaus CM, Ferreccio C, Romo JA, Yuan Y, Cortes S, Marshall G, et al. Drinking water arsenic in northern Chile: high cancer risks 40 years after exposure cessation. Cancer Epidemiol Biomark Prev. 2013;22(4):623–30.CrossRef
40.
41.
Chen CL, Chiou HY, Hsu LI, Hsueh YM, Wu MM, Chen CJ. Ingested arsenic, characteristics of well water consumption and risk of different histological types of lung cancer in northeastern Taiwan. Environ Res. 2010;110(5):455–62.PubMedCrossRef
42.
43.
44.
45.
De BK, Majumdar D, Sen S, Guru S, Kundu S. Pulmonary involvement in chronic arsenic poisoning from drinking contaminated ground-water. J Assoc Physicians India. 2004;52:395–400.PubMed
46.
Guha Mazumder DN. Arsenic and non-malignant lung disease. J Environ Sci Health A Tox Hazard Subst Environ Eng. 2007;42(12):1859–67.PubMedCrossRef
47.
48.
Waalkes M, Qu W, Tokar E, Kissling G, Dixon D. Lung tumors in mice induced by "whole-life" inorganic arsenic exposure at human-relevant doses. Arch Toxicol. 2014;88(8):1619–29.PubMedPubMedCentralCrossRef
49.
50.
51.
52.
53.
54.
Chen QY, Li J, Sun H, Wu F, Zhu Y, Kluz T, et al. Role of miR-31 and SATB2 in arsenic-induced malignant BEAS-2B cell transformation. Mol Carcinog. 2018;57(8):968–77.PubMedPubMedCentralCrossRef
55.
56.
Ling M, Li Y, Xu Y, Pang Y, Shen L, Jiang R, et al. Regulation of miRNA-21 by reactive oxygen species-activated ERK/NF-kappaB in arsenite-induced cell transformation. Free Radic Biol Med. 2012;52(9):1508–18.PubMedCrossRef
57.
Pratheeshkumar P, Son YO, Divya SP, Wang L, Zhang Z, Shi X. Oncogenic transformation of human lung bronchial epithelial cells induced by arsenic involves ROS-dependent activation of STAT3-miR-21-PDCD4 mechanism. Sci Rep. 2016;6:37227.PubMedPubMedCentralCrossRef
58.
59.
60.
61.
62.
Lee CH, Wu SB, Hong CH, Chen GS, Wei YH, Yu HS. Involvement of mtDNA damage elicited by oxidative stress in the arsenical skin cancers. J Invest Dermatol. 2013;133(7):1890–900.PubMedCrossRef
63.
64.
65.
Henderson MW, Madenspacher JH, Whitehead GS, Thomas SY, Aloor JJ, Gowdy KM, et al. Effects of orally ingested arsenic on respiratory epithelial permeability to bacteria and small molecules in mice. Environ Health Perspect. 2017;125(9):097024.PubMedPubMedCentralCrossRef
66.
67.
68.
69.
70.
Son YO, Pratheeshkumar P, Roy RV, Hitron JA, Wang L, Divya SP, et al. Antioncogenic and oncogenic properties of Nrf2 in arsenic-induced carcinogenesis. J Biol Chem. 2015;290(45):27090–100.PubMedPubMedCentralCrossRef
71.
Qi Y, Zhang M, Li H, Frank JA, Dai L, Liu H, et al. Autophagy inhibition by sustained overproduction of IL6 contributes to arsenic carcinogenesis. Cancer Res. 2014;74(14):3740–52.PubMedPubMedCentralCrossRef
72.
73.
74.
75.
Xu Y, Li Y, Pang Y, Ling M, Shen L, Yang X, et al. EMT and stem cell-like properties associated with HIF-2alpha are involved in arsenite-induced transformation of human bronchial epithelial cells. PLoS One. 2012;7(5):e37765.PubMedPubMedCentralCrossRef
76.
77.
78.
79.
80.
81.
Muenyi CS, Ljungman M, States JC. Arsenic disruption of DNA damage responses-potential role in carcinogenesis and chemotherapy. Biomolecules. 2015;5(4):2184–93.PubMedPubMedCentralCrossRef
82.
83.
Boellmann F, Zhang L, Clewell H, Schroth G, Kenyon E, Andersen M, et al. Genome-wide analysis of DNA methylation and gene expression changes in the mouse lung following subchronic arsenate exposure. Toxicol Sci. 2010;117(2):404–17.PubMedCrossRef
84.
Li M, Cai J, Chiu J. Arsenic induces oxidative stress and activates stress gene expressions in cultured lung epithelial cells. J Cell Biochem. 2002;87(1):29–38.PubMedCrossRef
85.
86.
Sherwood CL, Liguori AE, Olsen CE, Lantz RC, Burgess JL, Boitano S. Arsenic compromises conducting airway epithelial barrier properties in primary mouse and immortalized human cell cultures. PLoS One. 2013;8(12):e82970.PubMedPubMedCentralCrossRef
87.
88.
Tsou T, Yeh S, Tsai E, Tsai F, Chao H, Chang L. Arsenite enhances tumor necrosis factor-alpha-induced expression of vascular cell adhesion molecule-1. Toxicol Appl Pharmacol. 2005;209(1):10–8.PubMedCrossRef
89.
Kitchin K. Recent advances in arsenic carcinogenesis: modes of action, animal model systems, and methylated arsenic metabolites. Toxicol Appl Pharmacol. 2001;172(3):249–61.PubMedCrossRef
90.
91.
92.
93.
Mazumder D. Effect of chronic intake of arsenic-contaminated water on liver. Toxicol Appl Pharmacol. 2005;206(2):169–75.PubMedCrossRef
94.
95.
Orr S, Bridges C. Chronic kidney disease and exposure to nephrotoxic metals. Int J Mol Sci. 2017:18(5).
96.
Mochizuki H: Arsenic neurotoxicity in humans. Int J Mol Sci 2019, 20(14).
97.
IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Some drinking-water disinfectants and contaminants, including arsenic. IARC monographs on the evaluation of carcinogenic risks to humans. 2004; 84:1-477.
98.
Bozack AK, Saxena R, Gamble MV. Nutritional influences on one-carbon metabolism: effects on arsenic methylation and toxicity. Annu Rev Nutr. 2018;38:401–29.PubMedPubMedCentralCrossRef
99.
100.
Kenyon EM, Hughes MF, Adair BM, Highfill JH, Crecelius EA, Clewell HJ, et al. Tissue distribution and urinary excretion of inorganic arsenic and its methylated metabolites in C57BL6 mice following subchronic exposure to arsenate in drinking water. Toxicol Appl Pharmacol. 2008;232(3):448–55.PubMedCrossRef
101.
Hughes MF, Kenyon EM, Edwards BC, Mitchell CT, Razo LM, Thomas DJ. Accumulation and metabolism of arsenic in mice after repeated oral administration of arsenate. Toxicol Appl Pharmacol. 2003;191(3):202–10.PubMedCrossRef
102.
Naranmandura H, Chen X, Tanaka M, Wang WW, Rehman K, Xu S, et al. Release of apoptotic cytochrome C from mitochondria by dimethylarsinous acid occurs through interaction with voltage-dependent anion channel in vitro. Toxicol Sci. 2012;128(1):137–46.PubMedCrossRef
103.
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(3):192–205. https://​doi.​org/​10.​1002/​em.​10192.CrossRefPubMed
104.
105.
Yamanaka K, Kato K, Mizoi M, An Y, Takabayashi F, Nakano M, et al. The role of active arsenic species produced by metabolic reduction of dimethylarsinic acid in genotoxicity and tumorigenesis. Toxicol Appl Pharmacol. 2004;198(3):385–93.PubMedCrossRef
106.
107.
108.
109.
110.
Li K, Zhang L, Xiang X, Gong S, Ma L, Xu L, et al. Arsenic trioxide alleviates airway hyperresponsiveness and promotes apoptosis of CD4+ T lymphocytes: evidence for involvement of the ER stress-CHOP pathway. Ir J Med Sci. 2013;182(4):573–83.PubMedCrossRef
111.
Zhang L, Li K, Bing Ma L, Gong SB, Wang GY, Liu Y, et al. Effects and mechanism of arsenic trioxide on reversing the asthma pathologies including Th17-IL-17 axis in a mouse model. Iran J Allergy Asthma Immunol. 2012;11(2):133–45.PubMed
112.
Chu KH, Lee CC, Hsin SC, Cai BC, Wang JH, Chiang BL. Arsenic trioxide alleviates airway hyperresponsiveness and eosinophilia in a murine model of asthma. Cell Mol Immunol. 2010;7(5):375–80.PubMedPubMedCentralCrossRef
113.
114.
115.
116.
117.
Han YH, Kim SZ, Kim SH, Park WH. Arsenic trioxide inhibits the growth of Calu-6 cells via inducing a G2 arrest of the cell cycle and apoptosis accompanied with the depletion of GSH. Cancer Lett. 2008;270(1):40–55.PubMedCrossRef
118.
119.
120.
121.
122.
Wu P, Liu L, Weng J, Geng S, Deng C, Lu Z, et al. The synergistic effects of Decitabine combined with arsenic trioxide (ATO) in the human myelodysplastic syndrome cell line SKM-1. Indian J Hematol Blood Transfus. 2016;32(4):412–7.PubMedPubMedCentralCrossRef
123.
Peng X, Li W, Yuan L, Mehta RG, Kopelovich L, McCormick DL. Inhibition of proliferation and induction of autophagy by atorvastatin in PC3 prostate cancer cells correlate with downregulation of Bcl2 and upregulation of miR-182 and p21. PLoS One. 2013;8(8):e70442.PubMedPubMedCentralCrossRef
124.
125.
126.
127.
128.
Gu SY, Chen HY, Dai HM, Li XY, Zhang ZZ. miR-155/BACH1 signaling pathway in human lung adenocarcinoma cell death induced by arsenic trioxide. Sichuan Da Xue Xue Bao Yi Xue Ban. 2017;48(6):828–33.PubMed
129.
130.
131.
Klein CB, Leszczynska J, Hickey C, Rossman TG. Further evidence against a direct genotoxic mode of action for arsenic-induced cancer. Toxicol Appl Pharmacol. 2007;222(3):289–97.PubMedPubMedCentralCrossRef
132.
133.
134.
135.
136.
137.
138.
139.
140.
Jiang TT, Brown SL, Kim JH. Combined effect of arsenic trioxide and sulindac sulfide in A549 human lung cancer cells in vitro. J Exp Clin Cancer Res. 2004;23(2):259–62.PubMed
141.
Lam S, Leung L, Li Y, Zheng C, Ho J. Combination effects of arsenic trioxide and fibroblast growth factor receptor inhibitor in squamous cell lung carcinoma. Lung Cancer (Amsterdam, Netherlands). 2016;101:111–9.CrossRef
142.
Park H, Han B, Park W: Combination of arsenic trioxide and Valproic acid efficiently inhibits growth of lung cancer cells via G2/M-phase arrest and apoptotic cell death. Int J Mol Sci 2020, 21(7) 2649.
Metadata
Title
Paradoxical effects of arsenic in the lungs
Authors
Caixia Ren
Yang Zhou
Wenwen Liu
Qi Wang
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Environmental Health and Preventive Medicine / Issue 1/2021
Print ISSN: 1342-078X
Electronic ISSN: 1347-4715
DOI
https://doi.org/10.1186/s12199-021-00998-2

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