HYPOMETHYLATION OF DEOXYRIBONUCLEIC ACID IN TESTICULAR TISSUE DUE TO ARSENIC EXPOSURE IN MICE

Authors

  • Akhileshwari Nath
  • Priyanka
  • Aseem Kumar Anshu S S Hospital and Research Institute http://orcid.org/0000-0003-4878-0248
  • Chandan Kumar Singh
  • Sachidananda Behera
  • Jitendra Kumar Singh

DOI:

https://doi.org/10.22159/ajpcr.2016.v9s3.14932

Abstract

ABSTRACT
Objective: Among various environmental carcinogens, arsenic is highly sensitive and possesses potential to cause several diseases including cancer.
Nevertheless, arsenic has not been observed to induce mutation directly but is involved in epigenetic changes. Hypomethylation of oncogenes and
hypermethylation of tumor suppressor genes are reported to be associated with accumulation of arsenic. The present investigation demonstrates a
direct correlation arsenic and deoxyribonucleic acid (DNA) methylation.
Methods: Swiss albino mice were grouped as control and arsenic treated for 12 weeks. Arsenic concentration in blood and testes was analyzed by
atomic absorption spectrometer. Furthermore, DNA was extracted from the testes of mice by DNA purification kit and used for determining global
methylation in mice genome with the help of MethylFlash Methylated DNA Quantification Kit.
Results: Arsenic concentration in arsenic-treated mice was significantly higher than the control group in both blood and testes. Interestingly, arsenic
concentration in blood was recorded to be higher than testes in the arsenic-treated group with significance (p<0.0001). Moreover, a lower percentage
of cytosine of mice genome was found to be methylated in arsenic-treated mice group than control group (p<0.0001).
Conclusion: Greater concentration of arsenic in mice leads to hypomethylation of mice genome globally. Arsenic fosters deregulation of gene
expression by modifying methylation of CpG island of the promoter region. Epigenetic study is of prime importance in the field of oncology. Drug
development for repressing alteration of DNA methylation is imperative for cancer treatment.
Keywords: Arsenic, Cancer, Deoxyribonucleic acid, Methylation, Carcinogen.

Downloads

Download data is not yet available.

Author Biography

Aseem Kumar Anshu, S S Hospital and Research Institute

Junior Research Fellow, Research Institute, S S Hospital and Research Institute

References

IARC. Some Drinking-Water Disinfectants and Contaminants, Including Arsenic. Vol. 84. Geneva, Switzerland: WHO Press; 2004. Available from: http://www.monographs.iarc.fr/ENG/Monographs/vol84/index.php.

ATSDR. Toxicological Profile for Arsenic. GA, USA; Department of Health and Human Services, Public Health Service; 2007. Available from: http://www.atsdr.cdc.gov/toxprofiles/tp2.html.

Kesari VP, Kumar A, Khan PK. Induction of sperm impairments in mice as a sensitive biomarker of arsenic toxicity. Environ Monit Assess 2014;186(5):3115-21.

Chandra KA, Sengupta P, Goswami H, Sarkar M. Excessive dietary calcium in the disruption of structural and functional status of adult male reproductive system in rat with possible mechanism. Mol Cell Biochem 2012;364(1-2):181-91.

Buchet JP, Lauwerys R, Roels H. Comparison of the urinary excretion of arsenic metabolites after a single oral dose of sodium arsenite, monomethylarsonate, or dimethylarsinate in man. Int Arch Occup Environ Health 1981;48(1):71-9.

Lindgren A, Vahter M, Dencker L. Autoradiographic studies on the distribution of arsenic in mice and hamsters administered 74As-arsenite or - Arsenate. Acta Pharmacol Toxicol (Copenh) 1982;51(3):253-65.

Vahter M, Marafante E, Dencker L. Tissue distribution and retention of 74As-dimethylarsinic acid in mice and rats. Arch Environ Contam Toxicol 1984;13(3):259-64.

Benbrahim-Tallaa L, Waterland RA, Styblo M, Achanzar WE, Webber MM, Waalkes MP. Molecular events associated with arsenic-induced malignant transformation of human prostatic epithelial cells: Aberrant genomic DNA methylation and K-ras oncogene activation. Toxicol Appl Pharmacol 2005;206(3):288-98.

Zhao CQ, Young MR, Diwan BA, Coogan TP, Waalkes MP. Association of arsenic-induced malignant transformation with DNA hypomethylation and aberrant gene expression. Proc Natl Acad Sci U S A 1997;94(20):10907-12.

Stýblo M, Drobná Z, Jaspers I, Lin S, Thomas DJ. The role of biomethylation in toxicity and carcinogenicity of arsenic: A research update. Environ Health Perspect 2002;110 Suppl 5:767-71.

Yamauchi H, Fowler BA. Toxicity and metabolism of inorganic and methylated arsenicals. In: Nriagu JO, editor. Arsenic in the Environment, Part II: Human Health and Ecosystem Effects. New York: Wiley; 1994. p. 35-43.

Hirano S, Cui X, Li S, Kanno S, Kobayashi Y, Hayakawa T, et al. Difference in uptake and toxicity of trivalent and pentavalent inorganic arsenic in rat heart microvessel endothelial cells. Arch Toxicol 2003;77(6):305-12.

Esteller M. CpG island hypermethylation and tumor suppressor genes: A booming present, a brighter future. Oncogene 2002;21(35):5427-40.

Diala ES, Hoffman RM. Hypomethylation of HeLa cell DNA and the absence of 5-methylcytosine in SV40 and adenovirus (Type 2) DNA: Analysis by HPLC. Biochem Biophys Res Commun 1982;107(1):19-26.

Feinberg AP, Vogelstein B. Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature 1983;301(5895):89-92.

Bode AM, Dong Z. The paradox of arsenic: Molecular mechanisms of cell transformation and chemotherapeutic effects. Crit Rev Oncol Hematol 2002;42(1):5-24.

Okayasu R, Takahashi S, Sato H, Kubota Y, Scolavino S, Bedford JS. Induction of DNA double strand breaks by arsenite: Comparative studies with DNA breaks induced by X-rays. DNA Repair (Amst) 2003;2(3):309-14.

Marsit CJ, Karagas MR, Danaee H, Liu M, Andrew A, Schned A, et al. Carcinogen exposure and gene promoter hypermethylation in bladder cancer. Carcinogenesis 2006;27(1):112-6.

Chen H, Li S, Liu J, Diwan BA, Barrett JC, Waalkes MP. Chronic inorganic arsenic exposure induces hepatic global and individual gene hypomethylation: Implications for arsenic hepatocarcinogenesis. Carcinogenesis 2004;25(9):1779-86.

Rizki M, Kossatz E, Velázquez A, Creus A, Farina M, Fortaner S, et al. Metabolism of arsenic in Drosophila melanogaster and the genotoxicity of dimethylarsinic acid in the Drosophila wing spot test. Environ Mol Mutagen 2006;47(3):162-8.

Rossman TG, Stone D, Molina M, Troll W. Absence of arsenite mutagenicity in E coli and Chinese hamster cells. Environ Mutagen 1980;2(3):371-9.

Fischer JM, Robbins SB, Al-Zoughool M, Kannamkumarath SS, Stringer SL, Larson JS, et al. Co-mutagenic activity of arsenic and benzo [a] pyrene in mouse skin. Mutat Res 2005;588(1):35-46.

Singh KP, DuMond JW Jr. Genetic and epigenetic changes induced by chronic low dose exposure to arsenic of mouse testicular Leydig cells. Int J Oncol 2007;30(1):253-60.

Published

01-12-2016

How to Cite

Nath, A., Priyanka, A. K. Anshu, C. K. Singh, S. Behera, and J. K. Singh. “HYPOMETHYLATION OF DEOXYRIBONUCLEIC ACID IN TESTICULAR TISSUE DUE TO ARSENIC EXPOSURE IN MICE”. Asian Journal of Pharmaceutical and Clinical Research, vol. 9, no. 9, Dec. 2016, pp. 294-6, doi:10.22159/ajpcr.2016.v9s3.14932.

Issue

Section

Original Article(s)