Abstract
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.
Highlights
Cancer chemotherapy has the potential to produce acute and chronic damage in any organ system
Ocular toxicity induced by cancer chemotherapy is not uncommon, but the broad spectrum of reaction to injury displayed by the eye reflects the unique anatomical, physiological, and biochemical features of this essential organ
The control spectra degraded to eleven peaks and can be displayed into three regions 4000-3000 cm-1 that related to NHOH, 3000-2800 cm-1 that related to CH and 2000-1000 cm-1 that represent the fingerprint region
Summary
Cancer chemotherapy has the potential to produce acute and chronic damage in any organ system. Ocular toxicity induced by cancer chemotherapy is not uncommon, but the broad spectrum of reaction to injury displayed by the eye reflects the unique anatomical, physiological, and biochemical features of this essential organ. Tamoxifen (C26H29NO) is an antiestrogen therapy described for treatment of hormone receptor breast cancer [1]. It remains the first line pharmacological therapy for pre/peri-menopausal women and is often prescribed in the post-menopausal setting for patients at higher risk of osteoporosis or those who experienced significant side effects from aromatase inhibitors [2]. Tamoxifen can induce apoptosis in breast cancer cells via upregulation of pro-apoptotic factors, it can promote uterine hyperplasia in some women. The possible mechanism may be due to the protective effects against brain tissues oxidative damage
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