Effects of Boric Acid on ABL1 Gene Expression in Swiss Albino Mice Exposed to High-Dose Total Body Irradiation
DOI:
https://doi.org/10.58600/eurjther3044Keywords:
ABL1, boric acid, gene expression, total body irradiationAbstract
Objective: Radiation-induced DNA damage activates multiple cellular stress response pathways, including those associated with the ABL1 gene. This study investigated whether boric acid administration alters ABL1 gene expression following high-dose total body irradiation (TBI) in Swiss albino mice.
Methods: Seventy-two Swiss albino mice were allocated into control, radiotherapy (RT), boric acid (30, 100, or 300 mg/kg), and combined boric acid plus radiotherapy groups. Total body irradiation was delivered as a single 8 Gy dose on day 0. Boric acid was administered orally once daily, beginning two days prior to irradiation and continued until sacrifice on day 2 or day 6 post-irradiation. ABL1 gene expression levels were quantified by real-time polymerase chain reaction (RT-PCR), normalized to beta-actin (ACTB), and calculated using the 2⁻ΔΔCt method.
Results: ABL1 gene expression was elevated in irradiated groups compared with controls. A statistically significant increase was observed in the group receiving 100 mg/kg boric acid combined with RT on day 2 (p < 0.050). Although other treatment groups also demonstrated increased ABL1 expression, these differences were not statistically significant, which may be attributable to inter-individual variability.
Conclusion: Boric acid appears to modulate radiation-induced alterations in ABL1 gene expression in a dose- and time-dependent manner. The observed effects were more pronounced during the early post-irradiation period, suggesting a potential influence of boric acid on early molecular responses to radiation exposure.
References
[1] Saini S, Gurung P (2025) A comprehensive review of sensors of radiation-induced damage, radiation-induced proximal events, and cell death. Immunol Rev. 329(1):e13409. https://doi.org/10.1111/imr.13409
[2] Hu Z, Chen Y, Yang S, Diao S, Ma L, Shi C (2025) Radiation-induced biological effects: molecular and cellular mechanisms and applications to radiation/nuclear emergency and cancer therapy. MedComm. 6(12):e70478. https://doi.org/10.1002/mco2.70478
[3] Long F, Wang H, Sun Z, Yuan J (2025) BCR::ABL1-positive secondary B-acute lymphoblastic leukemia mimicking acute megakaryoblastic leukemia following multiple myeloma. Turk J Haematol. https://doi.org/10.4274/tjh.galenos.2025.2025.0277
[4] Kosik P, Skorvaga M, Belyaev I (2023) Preleukemic fusion genes induced via ionizing radiation. Int J Mol Sci. 24(7):6580. https://doi.org/10.3390/ijms24076580
[5] Vilar JB, Christmann M, Tomicic MT (2022) Alterations in molecular profiles affecting glioblastoma resistance to radiochemotherapy. Cancers (Basel). 14(10):2416. https://doi.org/10.3390/cancers14102416
[6] Cyran M, Stawarz K, Chambily L, Kusza K, Siemionow M (2024) Assessment of hematopoietic response to total body irradiation in a rat experimental model. Ann Plast Surg. 93(1):100–106. https://doi.org/10.1097/SAP.0000000000003962
[7] Liu R, Bian Y, Liu L, Liu X, Ma S (2022) Molecular pathways associated with oxidative stress and their potential applications in radiotherapy. Int J Mol Med. 49(5):65. https://doi.org/10.3892/ijmm.2022.5121
[8] Obrador E, Salvador-Palmer R, Villaescusa JI, Gallego E, Pellicer B, Estrela JM, et al. (2022) Nuclear and radiological emergencies: biological effects, countermeasures and biodosimetry. Antioxidants (Basel). 11(6):1098. https://doi.org/10.3390/antiox11061098
[9] Kumar R, Thakur A, Kumar S, Hajam YA (2024) Royal jelly as a promising therapeutic intervention and functional food supplement: a systematic review. Heliyon. 10(17):e37138. https://doi.org/10.1016/j.heliyon.2024.e37138
[10] Koldemir-Gündüz M, Aydin HE, Berikten D, Kaymak G, Köse DA, Arslantaş A (2021) Synthesis of new boron-derived compounds: anticancer, antioxidant and antimicrobial effects in vitro glioblastoma tumor model. J Korean Neurosurg Soc. 64(6):864–872. https://doi.org/10.3340/jkns.2021.0032
[11] Maliszewska-Olejniczak K, Kaniowski D, Araszkiewicz M, Tymińska K, Korgul A (2021) Molecular mechanisms of DNA damage response induced by mixed radiation fields during boron neutron capture therapy. Front Oncol. 11:676575. https://doi.org/10.3389/fonc.2021.676575
[12] Punshon LD, Fabbrizi MR, Phoenix B, Green S, Parsons JL (2024) Current insights into the radiobiology of boron neutron capture therapy and the potential for further improving biological effectiveness. Cells. 13(24):2065. https://doi.org/10.3390/cells13242065
[13] Skorski T (2002) BCR/ABL regulates response to DNA damage: role in resistance to genotoxic treatment and genomic instability. Oncogene. 21(56):8591–8604. https://doi.org/10.1038/sj.onc.1206087
[14] Matheson CJ, Venkataraman S, Amani V, Harris PS, Backos DS, Donson AM, et al. (2016) A WEE1 inhibitor analog of AZD1775 maintains synergy with cisplatin. ACS Chem Biol. 11(4):921–930. https://doi.org/10.1021/acschembio.5b00938
[15] Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods. 25(4):402–408. https://doi.org/10.1006/meth.2001.1262
[16] Malnassy G, Keating CR, Gad S, Bridgeman B, Perera A, Hou W, Cotler SJ, Ding X, Choudhry M, Sun Z, Koleske AJ, Qiu, W (2023) Inhibition of ABL2 suppresses alcohol-associated liver disease. Cell Mol Gastroenterol Hepatol. 16(5):685–709. https://doi.org/10.1016/j.jcmgh.2023.07.006
[17] Kosir R, Acimovic J, Golicnik M, Perse M, Majdic G, Fink M, Rozman D (2010) Determination of reference genes for circadian studies. BMC Mol Biol. 11:60. https://doi.org/10.1186/1471-2199-11-60
[18] Huang RX, Zhou PK (2020) DNA damage response signaling pathways and targets for radiotherapy sensitization. Signal Transduct Target Ther. 5(1):60. https://doi.org/10.1038/s41392-020-0150-X
[19] Olive PL (1998) The role of DNA single- and double-strand breaks in cell killing by ionizing radiation. Radiat Res. 150(Suppl 5):S42–S51. https://doi.org/10.2307/3579807
[20] Han W, Yu KN (2010) Ionizing radiation, DNA double strand breaks and mutation. In: Advances in Genetic Research, Vol. 4. Nova Science Publishers, New York, pp. 197–210.
[21] Hintelmann K, Kriegs M, Rothkamm K, Rieckmann T (2020) Improving tumor radiosensitization through combined molecular targeting. Front Oncol. 10:1260. https://doi.org/10.3389/fonc.2020.01260
[22] Gonfloni S (2010) DNA damage stress response in germ cells: role of c-Abl and clinical implications. Oncogene. 29(47):6193–6202. https://doi.org/10.1038/onc.2010.362
[23] Borlak J, Ciribilli Y, Bisio A, Selvaraj S, Inga A, Oh JH, Spanel R (2024) The Abl1 tyrosine kinase is a key player in doxorubicin-induced cardiomyopathy and its p53/p73 cell death mediated signaling differs in atrial and ventricular cardiomyocytes. J Transl Med. 22(1):845. https://doi.org/10.1186/s12967-024-05623-8
[24] Cruz-Garcia L, Nasser F, O’Brien G, Grepl J, Vinnikov V, Starenkiy V, Artiukh S, Gramatiuk S, Badie C (2022) Transcriptional dynamics of DNA damage-responsive genes during radiotherapy. Cancers (Basel). 14(11):2649. https://doi.org/10.3390/cancers14112649
[25] Kar F, Hacioglu C, Senturk H, Donmez DB, Kanbak G (2020) The Role of Oxidative Stress, Renal Inflammation, and Apoptosis in Post Ischemic Reperfusion Injury of Kidney Tissue: the Protective Effect of Dose-Dependent Boric Acid Administration. Biol Trace Elem Res. 195:150–158. https://doi.org/10.1007/s12011-019-01824-1
[26] Paganetti H (2023) Lymphocyte radiosensitivity and its impact on radiotherapy. Front Oncol. 13:1201500. https://doi.org/10.3389/fonc.2023.1201500
[27] Kim W, Lee S, Seo D, Kim D, Kim K, Kim E, Kang J, Seong KM, Youn H, Youn B (2019) Cellular stress responses in radiotherapy. Cells. 8(9):1105. https://doi.org/10.3390/cells8091105
[28] Bhattacharya S, Asaithamby A (2017) Repurposing DNA repair factors to eradicate tumor cells upon radiotherapy. Transl Cancer Res. 6(Suppl 5):S822–S830. https://doi.org/10.21037/tcr.2017.05.22
[29] Chen KH, Lai ZY, Li DY, Lin YC, Chou FI, Chuang YJ (2019) Analysis of DNA damage responses after boric acid-mediated boron neutron capture therapy in hepatocellular carcinoma. Anticancer Res. 39(12):6661–6671. https://doi.org/10.21873/anticanres.13881
[30] Bohio AA, Wang R, Zeng X, Ba X (2020) c-Abl-mediated tyrosine phosphorylation of DNA damage response proteins and implications in important cellular functions. Mol Med Rep. 22(2):612–619. https://doi.org/10.3892/mmr.2020.11156
[31] Garcia MEG, Kirsch DG, Reitman ZJ (2022) Targeting the ATM kinase to enhance the efficacy of radiotherapy and outcomes for cancer patients. Semin Radiat Oncol. 32(1):3–14. https://doi.org/10.1016/j.semradonc.2021.09.008
[32] Hak CMCW, Rullan A, Patin EC, Pedersen M, Melcher AA, Harrington KJ (2022) Enhancing anti-tumour innate immunity by targeting the DNA damage response and pattern recognition receptors in combination with radiotherapy. Front Oncol. 12:971959. https://doi.org/10.3389/fonc.2022.971959
[33] Chiu LY, Sun Q, Zenke FT, Blaukat A, Vassilev LT (2023) Selective ATM inhibition augments radiation-induced inflammatory signaling and cancer cell death. Aging (Albany NY). 15(2):492–505. https://doi.org/10.18632/aging.204487
Downloads
Published
How to Cite
Issue
Section
Categories
License
Copyright (c) 2026 Seda Ekici, Bekir Eren Çetin, Yasin Korucu, Akın Yiğin

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
The content of this journal is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.









