Abstract
Inorganic arsenic is considered as an environmental toxicant and Group I carcinogen. Globally millions of people are suffering from adverse health complications due to the contamination of arsenic in drinking water. Chronic exposure to arsenic results in the accumulation of arsenic and its metabolites in different cells and tissues. Increased concentration of cellular arsenic leads to the upregulation of oxidative stress and other toxic complications. Epidemiological studies evidenced that chronic exposure of arsenic in drinking water was related to the incidence of skin, lung, kidney, liver, and bladder cancers in certain regions of the world. Arsenic-induced reactive oxygen species (ROS) generation is considered as the initiator of its carcinogenic potential whereas; mitochondrial electron transport chain acts as the major source of arsenic-induced ROS production. Short-term exposure of arsenic-induced ROS upregulates inflammatory and pro-apoptotic pathways. But during prolonged exposure of arsenic-induced ROS generation was identified to be related to genotoxic and carcinogenic effects. However, there are many missing links in the switching between apoptotic to proliferative changes during prolonged arsenic exposure. The current chapter will focus to delineate how arsenic-induced ROS contributes to carcinogenesis. Furthermore, the understanding of the complex mechanism of arsenic-induced carcinogenesis may help to develop new diagnostic and therapeutic targets.
References
Ahmad S, Kitchin KT, Cullen WR (2000) Arsenic species that cause release of iron from ferritin and generation of activated oxygen. Arch Biochem Biophys 382:195–202
An Y, Gao Z, Wang Z, Yang S, Liang J, Feng Y, Kato K, Nakano M, Okada S, Yamanaka K (2004) Immunohistochemical analysis of oxidative DNA damage in arsenic-related human skin samples from arsenic-contaminated area of China. Cancer Lett 214:11–18. https://doi.org/10.1016/j.canlet.2004.04.005
Andrew AS, Burgess JL, Meza MM, Demidenko E, Waugh MG, Hamilton JW, Karagas MR (2006) Arsenic exposure is associated with decreased DNA repair in vitro and in individuals exposed to drinking water arsenic. Environ Health Perspect 114:1193–1198
Banerjee M, Bhattacharjee P, Giri AK (2011) Arsenic-induced cancers: a review with special reference to gene, environment and their interaction. Genes Environ 33:128–140
Carlin DJ, Naujokas MF, Bradham KD, Cowden J, Heacock M, Henry HF, Lee JS, Thomas DJ, Thompson C, Tokar EJ (2016) Arsenic and environmental health: state of the science and future research opportunities. Environ Health Perspect 124:890–899
Goussetis DJ, Platanias LC (2010) Arsenic trioxide and the phosphoinositide 3-kinase/akt pathway in chronic lymphocytic leukemia. Clin Cancer Res 16:4311–4312
Hayakawa T, Kobayashi Y, Cui X, Hirano S (2005) A new metabolic pathway of arsenite: arsenic–glutathione complexes are substrates for human arsenic methyltransferase Cyt19. Arch Toxicol 79:183–191
Hu Y, Li J, Lou B, Wu R, Wang G, Lu C, Wang H, Pi J, Xu Y (2020) The role of reactive oxygen species in arsenic toxicity. Biomol Ther 10:240,1–30
Hubaux R, Becker-Santos DD, Enfield KS, Rowbotham D, Lam S, Lam WL, Martinez VD (2013) Molecular features in arsenic-induced lung tumors. Mol Cancer 12:1–11
Hutchinson J (1887) An address on the study of skin diseases as illustrating the doctrines of general pathology. Br Med J 2:229
IARC Working Group on the Evaluation of Carcinogenic Risks to Humans (2004) Some drinking-water disinfectants and contaminants, including arsenic. IARC Monogr Eval Carcinog Risks Hum 84:1–477
Kitchin KT, Conolly R (2010) Arsenic-induced carcinogenesis: oxidative stress as a possible mode of action and future research needs for more biologically based risk assessment. Chem Res Toxicol 23:327–335
Kurttio P, Pukkala E, Kahelin H, Auvinen A, Pekkanen J (1999) Arsenic concentrations in well water and risk of bladder and kidney cancer in Finland. Environ Health Perspect 107:705–710
Lantz RC, Hays AM (2006) Role of oxidative stress in arsenic-induced toxicity. Drug Metab Rev 38:791–804
Lau A, Zheng Y, Tao S, Wang H, Whitman SA, White E, Zhang DD (2013) Arsenic inhibits autophagic flux, activating the Nrf2-Keap1 pathway in a p62-dependent manner. Mol Cell Biol 33:2436–2446. https://doi.org/10.1128/MCB.01748-12
Lemarie A, Bourdonnay E, Morzadec C, Fardel O, Vernhet L (2008) Inorganic arsenic activates reduced NADPH oxidase in human primary macrophages through a rho kinase/p38 kinase pathway. J Immunol 180:6010–6017. https://doi.org/10.4049/jimmunol.180.9.6010
Li L, Chen F (2016) Oxidative stress, epigenetics, and cancer stem cells in arsenic carcinogenesis and prevention. Curr Pharmacol Rep 2:57–63
Martinez VD, Vucic EA, Becker-Santos DD, Gil L, Lam WL (2011) Arsenic exposure and the induction of human cancers. J Toxicol 2011:431287,1–13
Mathews V, Paul M, Abhilash M, Manju A, Abhilash S, Nair RH (2013) Myocardial toxicity of acute promyelocytic leukaemia drug-arsenic trioxide. Eur Rev Med Pharmacol Sci 17:S34–S38
Mathews VV, Paul MS, Abhilash M, Manju A, Abhilash S, Nair RH (2014) Mitigation of hepatotoxic effects of arsenic trioxide through omega-3 fatty acid in rats. Toxicol Ind Health 30:806–813
Miller WH Jr, Schipper HM, Lee JS, Singer J, Waxman S (2002) Mechanisms of action of arsenic trioxide. Cancer Research 62:3893–3903
Minatel BC, Sage AP, Anderson C, Hubaux R, Marshall EA, Lam WL, Martinez VD (2018) Environmental arsenic exposure: from genetic susceptibility to pathogenesis. Environ Int 112:183–197
Mourón SA, Grillo CA, Dulout FN, Golijow CD (2006) Induction of DNA strand breaks, DNA-protein crosslinks and sister chromatid exchanges by arsenite in a human lung cell line. Toxicol In Vitro 20:279–285
Németi B, Regonesi ME, Tortora P, Gregus Z (2010) Polynucleotide phosphorylase and mitochondrial ATP synthase mediate reduction of arsenate to the more toxic arsenite by forming arsenylated analogues of ADP and ATP. Toxicol Sci 117:270–281
Rehman K, Naranmandura H (2013) Double-edged effects of arsenic compounds: anticancer and carcinogenic effects. Curr Drug Metab 14:1029–1041. https://doi.org/10.2174/13892002113146660116
Saint-Jacques N, Parker L, Brown P, Dummer TJ (2014) Arsenic in drinking water and urinary tract cancers: a systematic review of 30 years of epidemiological evidence. Environ Health 13:44
Sciandrello G, Caradonna F, Mauro M, Barbata G (2004) Arsenic-induced DNA hypomethylation affects chromosomal instability in mammalian cells. Carcinogenesis 25:413–417
Stýblo M, Drobná Z, Jaspers I, Lin S, Thomas DJ (2002) The role of biomethylation in toxicity and carcinogenicity of arsenic: a research update. Environ Health Perspect 110:767–771
Tchounwou PB, Yedjou CG, Udensi UK, Pacurari M, Stevens JJ, Patlolla AK, Noubissi F, Kumar S (2019) State of the science review of the health effects of inorganic arsenic: Perspectives for future research.  Environmental toxicology 34:188–202
Varghese MV, Manju A, Abhilash M, Paul MS, Abhilash S, Nair RH (2014) Oxidative stress induced by the chemotherapeutic agent arsenic trioxide. 3 Biotech 4:425–430
Varghese MV, Abhilash M, Paul MS, Alex M, Nair RH (2017a) Omega-3 fatty acid protects against arsenic trioxide-induced cardiotoxicity in vitro and in vivo. Cardiovasc Toxicol 17:109–119
Varghese MV, Abhilash M, Alex M, Paul MS, Prathapan A, Raghu K, Nair RH (2017b) Attenuation of arsenic trioxide induced cardiotoxicity through flaxseed oil in experimental rats. Redox Rep 22:346–352
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2021 Springer Nature Singapore Pte Ltd.
About this entry
Cite this entry
M, A., Ayyappan, P., R, H.N., Valuparampil Varghese, M. (2021). Arsenic: An environmental toxicant-induced oxidative stress and carcinogenesis. In: Chakraborti, S., Ray, B.K., Roychowdhury, S. (eds) Handbook of Oxidative Stress in Cancer: Mechanistic Aspects. Springer, Singapore. https://doi.org/10.1007/978-981-15-4501-6_40-1
Download citation
DOI: https://doi.org/10.1007/978-981-15-4501-6_40-1
Received:
Accepted:
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-15-4501-6
Online ISBN: 978-981-15-4501-6
eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences