Effect of azacytidine administration with/without folic acid on the histology and genomic DNA methylation of mice liver

Authors

  • Asal Aziz Tawfeeq Northern Technical University/ Technical College of Kirkuk Medical Laboratory Technique Department.

DOI:

https://doi.org/10.30574/gscbps.2020.11.2.0132

Keywords:

Azacytidine, Folic acid, Histology, Genomic DNA, Mice liver

Abstract

Azacitidine is a cytosine analog and antineoplastic agent used in the therapy of myelodysplastic syndromes with mild to moderate liver injuries. Accordingly, this research implicated to evaluate the epigenetic effect of azacytidine on mice liver as a model organism and to determine the role of folic acid administration as a protective methyl donor micronutrient. Thus, forty-eight mice were divided into four groups, reliant on the kind of treatment they received, where animals received calculated doses of azacytidine and folic acid twice a week for three months. Then, animals were killed, and their livers were autopsied and examined for histopathological abnormalities, followed by a genetic assessment for the DNA banding pattern profile of the excised livers. It was found that the anticancer drug azacytidine processes a hepatotoxic effect, and it profoundly modifies the DNA banding pattern. While the combination of folic acid with the administration of azacytidine might induce a protective effect against azacytidine toxic effects, these findings might unravel essential insights and highlight new potential cancer therapeutics.

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References

Veron V, Marandel L, Liu J, Vélez EJ, Lepais O, Panserat S, Skiba S and Seiliez I. (2018). DNA methylation of the promoter region of bnip3 and bnip3l genes induced by metabolic programming. BMC genomics, 19(1), 1-14.

McGee M, Bainbridge S and Fontaine-Bisson B. (2018). A crucial role for maternal dietary methyl donor intake in epigenetic programming and fetal growth outcomes. Nutrition reviews, 76(6), 469-478.

Ito H, Gaubert H, Bucher E, Mirouze M, Vaillant I and Paszkowski J. (2011). An siRNA pathway prevents transgenerational retrotransposition in plants subjected to stress. Nature, 472(7341), 115-119.

Silverman LR, Holland JF, Weinberg RS, Alter BP, Davis RB, Ellison RR, Demakos EP, Cornell JC, Carey RW and Schiffer C. (1993). Effects of treatment with 5-azacytidine on the in vivo and in vitro hematopoiesis in patients with myelodysplastic syndromes. Leukemia, 7, 21-29.

Athanasio CG, Sommer U, Viant MR, Chipman JK and Mirbahai L. (2018). Use of 5-azacytidine in a proof-of-concept study to evaluate the impact of pre-natal and post-natal exposures, as well as within generation persistent DNA methylation changes in Daphnia. Ecotoxicology, 27(5), 556-568.

Cabezón M, Bargay J, Xicoy B, García O, Borrás J, Tormo M, Marcé S, Pedro C, Valcárcel D, Jiménez MJ and Guàrdia R. (2018). Impact of mutational studies on the diagnosis and the outcome of high-risk myelodysplastic syndromes and secondary acute myeloid leukemia patients treated with 5-azacytidine. Oncotarget, 9(27), 19342.

Chang S and Pikaard CS. (2005). Transcript profiling in Arabidopsis reveals complex responses to global inhibition of DNA methylation and histone deacetylation. Journal of Biological Chemistry, 280(1), 796-804.

Pecinka A and Liu CH. (2014). Drugs for plant chromosome and chromatin research. Cytogenetic and genome research, 143(1-3), 51-59.

Askenazi DJ, Koralkar R, Patil N, Halloran B, Ambalavanan N and Griffin R. (2016). Acute kidney injury urine biomarkers in very low-birth-weight infants. Clinical Journal of the American Society of Nephrology, 11(9), 1527-1535.

Gillberg L, Ørskov AD, Nasif A, Ohtani H, Madaj Z, Hansen JW, Rapin N, Mogensen JB, Liu M, Dufva IH and Lykkesfeldt J. (2019). Oral vitamin C supplementation to patients with myeloid cancer on azacitidine treatment: Normalization of plasma vitamin C induces epigenetic changes. Clinical epigenetics, 11(1), 1-11.

Kaminskas E, Farrell A, Abraham S, Baird A, Hsieh LS, Lee SL, Leighton JK, Patel H, Rahman A, Sridhara R and Wang YC. (2005). Approval summary: azacitidine for treatment of myelodysplastic syndrome subtypes. Clinical cancer research, 11(10), 3604-3608.

Estey EH. (2013). "Epigenetics in clinical practice: the examples of azacitidine and decitabine in myelodysplasia and acute myeloid leukemia". Leukemia, 27(9), 1803–12.

Mahmoud AM and Ali MM. (2019). Methyl donor micronutrients that modify DNA methylation and cancer outcome. Nutrients, 11(3), 608.

Müller A and Florek M. (2010). 5-azacytidine/Azacitidine. In Small Molecules in Oncology, 159-170.

Tawfeeq AA. (2014). Effect of Kaff Maryam aqueous extract in mice Kidneys. karbala journal of pharmaceutical sciences, (7), 123-130.

Argemí A, Vega A, Subra-Paternault P and Saurina J. (2009). Characterization of azacytidine/poly (l-lactic) acid particles prepared by supercritical antisolvent precipitation. Journal of pharmaceutical and biomedical analysis, 50(5), 847-852.

Hernández-Díaz S, Werler MM, Walker AM and Mitchell AA. (2000). Folic acid antagonists during pregnancy and the risk of birth defects. New England journal of medicine, 343(22), 1608-1614.

Gibb H, Haver C, Gaylor D, Ramasamy S, Lee JS, Lobdell D, Wade T, Chen C, White P and Sams R. (2011). Utility of recent studies to assess the National Research Council 2001 estimates of cancer risk from ingested arsenic. Environmental health perspectives, 119(3), 284-290.

Bigatti E, Lux G and Paiocchi M. (2010). Process for preparing azacytidine intermediate. U.S. Patent Application 12/536,923.

Tawfeeq AA. (2005). Developmental effects of 5-azacytidine and folic acid on mice. PhD. Thesis, Al-Nahrain University, Iraq, 112-119.

FDA U. (2005). Guidance for industry. Estimating the maximum safe starting dose in initial clinical trials for therapeutics in adult healthy volunteers. FDA, ed.

Le T, Kim KP, Fan G and Faull KF. (2011). A sensitive mass spectrometry method for simultaneous quantification of DNA methylation and hydroxymethylation levels in biological samples. Analytical biochemistry, 15, 412(2), 203-9.

Enan MR. (2006). Application of random amplified polymorphic DNA (RAPD) to detect the genotoxic effect of heavy metals. Biotechnology and applied biochemistry, 43(3), 147-54.

Lammers PE and Cashen AF. (2009). Azacitidine: A Review of its Use in the Management of Myelodysplastic syndromes. Clinical Medicine. Therapeutics, 1, CMT-S1163.

Gailhouste L, Liew LC, Yasukawa K, Hatada I, Tanaka Y Nakagama H and Ochiya T. (2018). Differentiation therapy by epigenetic reconditioning exerts antitumor effects on liver cancer cells. Molecular Therapy, 26(7), 1840-1854.

Gailhouste L, Liew LC, Hatada I, Nakagama H and Ochiya T. (2018). Epigenetic reprogramming using 5-azacytidine promotes an anticancer response in pancreatic adenocarcinoma cells. Cell death & disease, 9(5), 1-12.

Ebaid H, Bashandy SA, Alhazza IM, Rady A and El-Shehry S. (2013). Folic acid and melatonin ameliorate carbon tetrachloride-induced hepatic injury, oxidative stress and inflammation in rats. Nutrition & metabolism, 10(1), 20.

Kiziltepe T, Hideshima T, Catley L, Raje N, Yasui H, Shiraishi N, Okawa Y, Ikeda H, Vallet S, Pozzi S and Ishitsuka K. (2007). 5-Azacytidine, a DNA methyltransferase inhibitor, induces ATR-mediated DNA double-strand break responses, apoptosis, and synergistic cytotoxicity with doxorubicin and bortezomib against multiple myeloma cells. Molecular cancer therapeutics, 6(6), 1718-1727.

Poirier S, Samami S, Mamarbachi M, Demers A, Chang TY, Vance DE, Hatch GM and Mayer G. (2014). The epigenetic drug 5-azacytidine interferes with cholesterol and lipid metabolism. Journal of biological chemistry, 289(27), 18736-18751.

Barnett MP, Bermingham EN, Young W, Bassett SA, Hesketh JE, Maciel-Dominguez A, McNabb WC and Roy NC, (2015). Low folate and selenium in the mouse maternal diet alters liver gene expression patterns in the offspring after weaning. Nutrients, 7(5), 3370-3386.

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Published

2020-05-30

How to Cite

Tawfeeq , A. A. (2020). Effect of azacytidine administration with/without folic acid on the histology and genomic DNA methylation of mice liver. GSC Biological and Pharmaceutical Sciences, 11(2), 196–203. https://doi.org/10.30574/gscbps.2020.11.2.0132

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Original Article