FTIR SPECTROSCOPIC TRENDS AND DNA DAMAGE IN RABBIT LENS DUE TO LONG RUN OF TAMOXIFEN TREATMENT
DOI:
https://doi.org/10.22159/ijap.2019v11i5.34109Keywords:
Chemotherapy, Tamoxifen, Lens, Cataract, FTIR, Comet assayAbstract
Objective: The aim of the present work is to evaluate the molecular structure changes of the lens of rabbits and DNA damage of epithelial cells due to tamoxifen administration.
Methods: Twenty four healthy New Zealand white rabbits were divided into 2 main groups. The first group is served as control (n=12) kept untreated, second one is Tamoxifen administrative group (n=12) received orally daily dose of 15 mg/kg. Rabbits were decapitated after 2, 4, 6 and 8 mo, respectively. Using fourior transform infrared (FTIR) to study the molecular structure changes due to tamoxifen and comet assay analysis for discovering DNA damage.
Results: FTIR data indicated that tamoxifen affects structural components in NHOH and fingerprint region. Increases of β-turns of the protein secondary structure while, reducing the content of both α-helix after 8 mo and Turns appeared for all periods of administrative tamoxifen were observed. On the other hand tamoxifen induced a statistically significant increase in comet assay parameters as tail moment compared to control animals that indicated DNA damage due to single or double strand break.
Conclusion: Tamoxifen uses for more than 6 mo may lead to changes in the molecular structure of the lens and damage of DNA cells. An ophthalmic baseline examination prior to anti-cancer treatment may help detect any pre-existing ocular condition and lead to reduction of ocular side effects when predisposed patients are screened and examined regularly during and after chemotherapeutic therapy.
Downloads
References
Ursulovic T, Milovanovic Z, Medic Milijic N, Gavrilovic D, Plesinac Karapandzic V, Susnjar S. The influence of PTEN protein expression on disease outcome in premenopausal hormone receptor-positive early breast cancer patients treated with adjuvant ovarian ablation: a long-term follow-up. J BUON 2018;23:902-9.
Jansen LE, Teft WA, Rose RV, Lizotte DJ, Kim RB. CYP2D6 genotype and endoxifen plasma concentration do not predict hot flash severity during tamoxifen therapy. Breast Cancer Res Treat 2018;171:701-8.
Rouhimoghadam M, Safarian S, Carroll JS, Sheibani N, Bidkhori G. Tamoxifen-induced apoptosis of MCF-7 Cells via GPR30/PI3K/MAPKs interactions: verification by ODE modeling and RNA sequencing. Front Physiol 2018;9:907.
Tajik A, Rezayof A, Ghasemzadeh Z, Sardari M. Activation of the dorsal hippocampal nicotinic acetylcholine receptors improves tamoxifen-induced memory retrieval impairment in adult female rats. Neuroscience 2016;327:1-9.
Aytekin A, Bilgetekin I, Ciltas A, Ogut B, Coskun U, Benekli M. Lobular breast cancer metastasis to uterus during adjuvant tamoxifentreatment: a case report and review of the literature. J Cancer Res Ther 2018;14:1135-7.
Doshi R, Fortun J, Kim B, Dubovy S, Rosenfeld B. Pseudocystic foveal cavitation in tamoxifen retinopathy. Am J Ophthalmol 2014;157:1291-8.
Cho KS, Yoon YH, Choi JA, Lee SJ, Koh JY. Induction of autophagy and cell death by tamoxifen in cultured retinal pigment epithelial and photoreceptor cells. Invest Ophthalmol Vis Sci 2012;53:5344-53.
Eisner A, Luoh S. Breast cancer medications and vision: effects of treatments for early-stage disease. Curr Eye Res 2011;36:867-85.
Chung H, Kim D, Ahn S, Gone Kim J, Lee J, Lim J, et al. Early detection of tamoxifen-induced maculopathy in patients with low cumulative doses of tamoxifen. Ophthalmic Surgery, Lasers and Imaging Retina; 2010.
Parkkari M, Paakkala A, Salminen L, Holli K. Ocular side‐effects in breast cancer patients treated with tamoxifen and toremifene: a randomized follow‐up study. Acta Ophthalmol Scandina Vica 2003;81:495-9.
Greaves P, Goonetilleke R, Nunn G, Topham J, Orton T. Two-year carcinogenicity study of tamoxifen in Alderley Park Wistar-derived rats. J Cancer Res 1993;53:3919-24.
Eman MA, Mervat AA. Effects of bilberry on deoxyribonucleic acid damage and oxidant-antioxidant balance in the lens, Induced by Ultraviolet Radiation. Malays J Med Sci 2014;21:11-8.
Eman M. Ftir analysis for retina associated with diabetic changes and treatment with oat. Int J Pharm Pharm Sci 2015;7:277-80.
Janakiraman M. Protective efficacy of silver nanoparticles synthesized from silymarin on cisplatin induced renal oxidative stress in albino rat. Int J Appl Pharm 2018;10:110-6.
Loffhagen N, Hartig C, Geyer W, Voyevoda M, Harms H. Competition between cis, trans, and cyclopropane fatty acid formation and its impact on membrane fluidity. Eng Life Sci 2007;7:67–74.
Sato ET, Martinho H. First-principles calculations of Raman vibrational modes in the fingerprint region for connective tissue. Biomed Opt Express 2018;9:1728–34.
Lin SY, Li MJ, Liang RC, Lee SM. Non-destructive analysis of the conformational changes in human lens lipid and protein structures of the immature cataracts associated with glaucoma. Spectrochim Acta A Mol Biomol Spectrosc 1998;54A:1509-17.
Paluszkiewicz C, Piergies N, Sozanska A, Chaniecki P, Rękas M, Miszczyk J, et al. Vibrational microspectroscopy analysis of human lenses. Spectrochim Acta A Mol Biomol Spectrosc 2018;188:332-7.
White IN, de Matteis F, Davies A, Smith L, Crofton Sleigh C, Venitt S, et al. Genotoxic potential of tamoxifen and analogues in female Fischer F344/n rats, DBA/2 and C57BL/6 mice and in human MCL-5 cells. Carcinogenesis 1992;13:2197-203.
Zhang JJ, Jacob TJ, Valverde MA, Hardy SP, Mintenig GM, Sepulveda FV, et al. Tamoxifen blocks chloride channels. A possible mechanism for cataract formation. J Clin Invest 1994;94:1690-7.
Published
How to Cite
Issue
Section
