IIARD International Institute of Academic Research and Development

INTERNATIONAL JOURNAL OF MEDICAL EVALUATION AND PHYSICAL REPORT (IJMEPR )

E-ISSN 2579-0498
P-ISSN 2695-2181
VOL. 7 NO. 4 2023
DOI: 10.56201/ijmepr.v7.no4.2023.pg164.172

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Epigenetic Mechanisms in Metal Carcinogenesis (Article Review)

Sarah Ali Abed

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Abstract

Although carcinogenic metals have been demonstrated to disrupt a number of biological processes, the precise mechanism by which they cause cancer is uncertain. Research over the past decade or so suggests that epigenetic mechanisms may play a role in metal-induced carcinogenesis. This paper compiles evidence that exposure to carcinogenic metals, including nickel, arsenic, chromium, and cadmium, can change worldwide and gene-specific histone tail posttranslational modification marks and DNA methylation levels. Additionally, we would like to stress the significance of comprehending that both genetic and epigenetic mechanisms can regulate gene expression, and that both of these need to be taken into account when researching the mechanisms behind the toxicity and cell-transforming potential of carcinogenic metals and other toxicants, as well as aberrant changes in gene expression that take place during disease states like cancer.

keywords:

DNA, Cancer, metal, Active, DNA Methylation, Global Hypomethylation Promoter Hyper, methylation, Histone Modifications

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References:

:
1- Paithankar JG, Saini S, Dwivedi S, Sharma A, Chowdhuri DK. Heavy metal associated
health hazards: An interplay of oxidative stress and signal transduction. Chemosphere.
2021;262:128350.
2- He ZL, Yang XE, Stoffella PJ. Trace elements in agroecosystems and impacts on the
environment. J Trace Elem Med Biol. 2005;19(2–3):125–140.
3- Zhao L, Islam R, Wang Y, Zhang X, Liu LZ. Epigenetic regulation in chromium-, nickel-
and cadmium-induced carcinogenesis. Cancers. 2022;14(23):5768.
4- Renu K, Chakraborty R, Myakala H, Koti R, Famurewa AC, Madhyastha H, Vellingiri B,
George A, Valsala Gopalakrishnan A. molecular mechanism of heavy metals (Lead,
Chromium, Arsenic, Mercury, Nickel and Cadmium)-induced hepatotoxicity—A review.
Chemosphere. 2021;271:129-137.
5- International Agency for Research on Cancer (IARC): Working Group on the Evaluation
of Carcinogenic Risks to Humans. Arsenic, metals, fibres, and dusts. A Review of Human
Carcinogens. Lyon, France. 2012;1-52.
6- Islam R, Zhao L, Wang Y, Lu-Yao G, Liu LZ. Epigenetic dysregulations in arsenic-
induced carcinogenesis. Cancers. 2022;14(18):4502.
7- World Health Organization. Cancer. [Internet]. 2023 [cited 2023 Oct 6].
8- Available:https://www.who.int/health-topics/cancer#tab=tab_1
9- Kim HS, Kim YJ, Seo YR. An overview of carcinogenic heavy metal: Molecular toxicity
mechanism and prevention. J Cancer Prev. 2015;20:232–240.
10- Baylin SB, Ohm JE. Epigenetic gene silencing in cancer – a mechanism for early oncogenic
pathway addiction? Nat Rev Cancer. 2006;6(2):107–116.
11- Martinez-Zamudio R, Ha HC. Environmental epigenetics in metal exposure. Epigenetics.
2011;6:820–827.
12- Kanwal R, Gupta S. Epigenetic modifications in cancer. Clin Genet. 2012;81(4):303–311.
13- Mani? L, Wallace D, Onganer PU, Taalab YM, Farooqi AA, Antonijevi? B, Djordjevic
AB. Epigenetic mechanisms in metal carcinogenesis. Toxicol Rep. 2022;9:778-787.
14- Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Piñeros M. Global cancer observatory:
Cancer today. Lyon: International Agency for Research on Cancer. [Internet]. 2020 [cited
2021 Feb].Available:https://gco.iarc.fr/today.
15- American Cancer Society. The Cancer Atlas. The Burden of Cancer. [Internet]. 2022 [cited
2022 Jan]. Available:The Cancer Atlas website
16- Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global
Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for
36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209–249.
17- World Health Organization. Cancer. [Internet]. 2022 [cited 2022]. Available from:
18- Allis CD, Jenuwein T. The molecular hallmarks of epigenetic control. Nat Rev Genet.
2016;17:487-500.
19- Wang B, Li Y, Shao C, Tan Y, Cai L. Cadmium and its epigenetic effects. Curr Med Chem.
2012;19:2611-20.
20- Henikoff S, Greally JM. Epigenetics, cellular memory and gene regulation. Curr Biol.
2016;26(14):R644-8.
21- Moore
LD,
Le
T,
Fan
G.
DNA
methylation
and
its
basic
function.
Neuropsychopharmacology. 2013;38(1):23-38.
22- Kaplun DS, Kaluzhny DN, Prokhortchouk EB, Zhenilo SV. DNA methylation:
genomewide distribution, regulatory mechanism and therapy target. Acta Naturae.
2022;14(4):4-19.
23- McMahon KW, Karunasena E, Ahuja N. The Roles of DNA Methylation in the Stages of
Cancer. Cancer J. 2017;23(5):257-61.
24- Nevin C, Carroll M. Sperm DNA Methylation, Infertility and Transgenerational
Epigenetics. J Hum Genet Clin Embryol. 2015;1.
25- Cox M, Nelson DR, Lehninger AL. Lehninger Principles of Biochemistry. W.H. Freeman;
26- Audia JE, Campbell RM. Histone Modifications and Cancer. Cold Spring Harb Perspect
Biol. 2016;8:19-34.
27- Bannister AJ, Kouzarides T. Regulation of chromatin by histone modifications. Cell Res.
2011;21:381–395.
28- Greer EL, Shi Y. Histone methylation: A dynamic mark in health, disease, and inheritance.
Nat Rev Genet. 2012;13:343–357.
29- Kouzarides T. Chromatin Modifications and Their Function. Cell. 2007;128:693–705.
30- Renaude E, Marie K, Borg C, Peixoto P, Hervouet E, Loyon R, et al. Epigenetic
reprogramming of CD4+ Helper T cells as a strategy to improve anticancer
immunotherapy. Front Immunol. 2021;12:669992.
31- Morris KV (Ed.). Non-coding RNAs and Epigenetic Regulation of Gene Expression:
Drivers of Natural Selection. Caister Academic Press; 2012.
32- Yan H, Bu P. Non-coding RNA in cancer. Essays Biochem. 2021;65:625–639.
33- P. Sen and M. Costa, Induction of chromosomal damage in Chinese Hamster Ovary cells
by soluble and particulate nickel compounds: preferential fragmentation of the
heterochromatic long arm of the X-chromosome by carcinogenic crystalline NiS
particles, Cancer Res., 1985, 45, 2330–2325.
34- W. Lee, C. Klein, B. Kargacin, K. Salnikow, J. Kitahara, K. Dowjat, A. Zhitkovich, T.
Christie and M. Costa, Carcinogenic nickel silences gene expression by chromatin
condensation and DNA methylation: a new model for epigenetic carcinogens, Mol. Cell.
Biol., 1995, 15, 2547–2557 CAS .
35- B. Govindarajan, R. Klafter, M. Miller, C. Mansur, M. Mizesko, X. Bai, K. LaMotagne
and J. Arbiser, Reactive oxygen-induced carcinogenesis cause hypermethylation of p16
(Ink4a) and activation of MAP kinase, Mol. Med., 2002, 8, 1–8 CAS .
36- M. Costa, K. Salnikow, S. Consentino, C. Klein, X. Huang and Z. Zhuang, Molecular
mechanisms of nickel carcinogenesis, Environ. Health Perspect., 1991, 102, 127–130.
37- K. Conway, X. Wang, L. Xu and M. Costa, Effect of magnesium on nickel-induced
genotoxicity
and
cell
transformation, Carcinogenesis,
1987, 8,
1115–
1121 CrossRef CAS .
38- N. Borochov, J. Ausio and H. Eisenberg, Interaction and conformational changes of
chromatin with divalent ions, Nucleic Acids Res., 1984, 12, 3089–3096 CrossRef CAS .
39- A. Karaczyn, F. Golebiowski and K. S. Kasprzak, Truncation, deamidation and oxidation
of histone H2B in cells cultured with nickel(II), Chem. Res. Toxicol., 2005, 18, 1934–
1942 CrossRef CAS .
40- A. Karaczyn, S. Ivanov, M. Reynolds, A. Zhitkovich, K. S. Kasprzak and K. Salnikow,
Ascorbate depletion mediates up-regulation of hypoxia-associated proteins by cell density
and nickel, J. Cell. Biochem., 2006, 97, 1025–1035 CrossRef CAS .
41- L. Broday, W. Peng, M. H. Kuo, K. Salnikow, M. Zoroddu and M. Costa, Nickel
compounds are novel inhibitors of histone H4 acetylation, Cancer Res., 2000, 60, 238–
241 CAS .
42- H. Chen, Q. Ke, T. Kluz, Y. Yan and M. Costa, Nickel ions increase histone H3 lysine 9
dimethylation and induce transgene silencing, Mol. Cell. Biol., 2006, 26, 3728–
3737 CrossRef CAS .
43- Q. Ke, T. Davidson, H. Chen, T. Kluz and M. Costa, Alterations of histone modifications
and transgene silencing by nickel chloride, Carcinogenesis, 2006, 27, 1481–
1488 CrossRef CAS .
44- F. Golebiowski and K. S. Kasprzak, Inhibition of core histones acetylation by carcinogenic
nickel(II), Mol. Cell. Biochem., 2005, 279, 133–139 CrossRef CAS .
45- C. Klein and M. Costa, DNA methylation, heterochromatin and epigenetic
carcinogens, Mutat. Res., 1997, 386, 163–80 CAS .
46- C. Klein, K. Conway, X. Wang, K. Bhamra, X. Lin, M. Cohen, L. Annab, J. Barrett and
M. Costa, Senescence of nickel-transformed cells by an X-chromosome: possible
epigenetic control, Science, 1991, 251, 796–799 CrossRef CAS .
47- Y. Yan, T. Kluz, P. Zhang, H. Chen and M. Costa, Analysis of specific lysine histone H3
and H4 acetylation and methylation status in clones of cells with a gene silenced by nickel
exposure, Toxicol. Appl. Pharmacol., 2003, 190, 272–277 CrossRef CAS .
48- Q. Zhang, K. Salnikow, T. Kluz, L. Chen, W. Su and M. Costa, Inhibition and reversal of
nickel-induced transformation by the.

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