Effect of Dose Irradiation on the Expression of BRCA1 and BRCA2Genes in MCF-10A and MCF-7 cell lines

Introduction: Breast cancer can be caused by a mutation in its genome. Some mutations are cancer-predisposition which exist at the moment of germ cell genesis. It has been discovered that BRCA1 and BRCA2 are linked to hereditary breast cancer. BRCA1/2 are tumor suppressor genes involved in DNA repair and transcriptional regulation in response to DNA damage. Irradiation, particularly ionizing radiation used in clinical radiotherapy, causes DNA damage. This study aims to find out whether different doses of x-radiation might change the expression of BRCA1/2. Material and Methods: Cancer and normal breast cell lines (MCF10-A and MCF7) cultured in flasks were irradiated with X- rays in different doses including 50, 100, 400, 2000, and 4000 mGy. Then, the expression of BRCA1/2 genes was measured using real-time quantitative reverse transcription PCR (RT-qPCR). Relative changes for mRNA were calculated based on the ∆∆Ct method. Results: MCF-10A cells represent a significant increase in BRCA2 expression at all irradiation doses while increasing the mRNA level for the BRCA1 gene observed after exposure to 50, 100, and 2000 mGy. This figure shows overexpression of BRCA2 gene after all irradiation doses except 100 mGy for MCF7 cells. The BRCA1 gene upregulated after exposure to 400 and 2000 mGy and downregulated at 50,100 and 4000 mGy in these cells. Conclusion: Incidence of cancer initiation was probable in normal breast cells after low-dose radiation, with up-regulation of BRCA1 and BRCA2 gene expression. BRCA mutation may be an inadequate outcome predictor of survival rate and other factors may be involved too

Oral administration of melatonin modulates the expression of tumor necrosis factor-α (TNF-α) gene in irradiated rat cervical spinal cord

AimWe aimed to determine the changes in TNF-α expression and Malondialdehyde (MDA) level in a short time after irradiation. Furthermore, we evaluated the effect of melatonin on the modulation of TNF-α gene expression.BackgroundThe radio-sensitivity of the cervical spinal cord limits the dose of radiation which can be delivered to tumors in the neck region. There is increasing evidence that TNF-α has a role in the development of the acute phase of spinal cord injury.Materials/MethodsFour groups of rats were investigated. Group 1 (vehicle treatment) served as the control. Group 2 (radiation) was treated with the vehicle, and 30[[ce:hsp sp="0.25"/]]min later, the rats were exposed to radiation. Group 3 (radiation[[ce:hsp sp="0.25"/]]+[[ce:hsp sp="0.25"/]]melatonin) was given an oral administration of melatonin (100[[ce:hsp sp="0.25"/]]mg/kg body weight) and 30[[ce:hsp sp="0.25"/]]min later exposed to radiation in the same manner as in group 2. Group 4 (melatonin-only) was also given an oral administration of melatonin (100[[ce:hsp sp="0.25"/]]mg/kg body weight). 5[[ce:hsp sp="0.25"/]]mg/kg of melatonin was administered daily to rats in groups 3 and 4, and the vehicle was administered daily to rats in groups 1 and 2.ResultsThree weeks after irradiation, TNF-α gene up-regulated almost 5 fold in the irradiated group compared to the normal group. TNF-α gene expression in the melatonin pretreatment group, compared to the radiation group, was significantly down-regulated 3 weeks after irradiation (p[[ce:hsp sp="0.25"/]

In Vivo Mechanisms of Radioadaptive Response

Background & Objectives: Radioadaptive response (RAR) describes a phenomenon in which small priming doses of ionizing radiation (IR) reduce detrimental effects of subsequent higher doses. Since IR-induced carcinogenesis is a main concern in the low-dose radiation risk assessmen, the aim of this study was to investigate the RAR with the end points of carcinogenesis and the related genomic damages and evaluation of the effective in-vivo mechanisms in this phenomenon. Materials & Methods: The present review article was performed by using the research and review articles indexed in Pubmed, Google scholar, Science direct. In this review article, some resent studies related to RAR with end points of carcinogenesis in different species of mice and human lymphocytes has been investigated. Additionally, in the present review article, the role of important in vivo mechanisms involved in adaptive response, namely DNA repair, bystander effect and endocrine system hormones such as glucocorticoids has been investigated. Results: These studies, often revealed efficient induction of RAR by chronic or repeated low-dose priming irradiation. Conclusion: Current radiation protection regulations do not include RAR because of the large variability in expression among individuals and uncertainties of the mechanism. However, in the future, RAR should be regarded as an indispensable factor for estimation and control of individual IR sensitivity

Hesperidin as a natural Radio-Protector

Despite widespread usage of ionizing radiation in medical diagnosis and treatment methods, development of radio-protective agents is important in modulating normal tissue damages. The inherent toxicity of synthetic compounds and the confirmation of low toxicity of natural compound in accordance with long – term usage of medicine have led many researchers to investigate the radio-protective abilities of natural compounds. Hesperidin (HES) is a flavanone glycoside, belonging to the flavonoid family found in human diet abundantly and noted for its many beneficial effects. However, hesperidin has fewer protective effects than synthetic compounds and less toxicity and possibility of oral administration. That is why it can be offered as a suitable radio-protector in radiotherapy patients, radiation workers, astronauts, and the public

Expression of Bax and Bcl2 genes in peripheral blood lymphocytes of patients with differentiated thyroid cancer

Context: Thyroid cancer is the most common endocrine malignancy worldwide. Iodine-131 is used in the treatment of thyroid cancer with dosage of 100 mCi. In the medical applications of ionizing radiation besides the advantages such as diagnosis and treatment of diseases, the risks arising from exposure should be considered as well. Aims: The present study aimed to evaluate the changes in expression levels of apoptotic Bax and Bcl-2 and the ratio of Bax/Bcl-2, in the peripheral blood lymphocytes (PBLs) of patients with differentiated thyroid cancer (DTC). Settings and Design: This study was conducted on fifty thyroid cancer patients who had undergone surgery and were under treatment with 100 and 150 mCi doses. Subjects and Methods: Blood samples were taken from the patients, one before iodine treatment and another 48 h after therapy. Bax and Bcl-2 gene expression levels were measured by using real-time reverse transcriptase polymerase chain reaction. Statistical Analysis Used: The data were analyzed using one-way analysis of variance followed by samples t-test and independent samples t-test. Results: Significant changes were observed in the percentage of apoptotic cells, in groups, after radioiodine therapy compared with before treatment. The ratio of Bax/Bcl-2 in both groups showed a significant increase (P < 0.001). The relative expression level of Bax gene showed a significant increase in comparison with the control group. Conclusions: Iodine therapy reduced expression of Bcl-2 and a significant expression of Bax and finally increased the ratio of Bax/Bcl-2. Iodine therapy led to apoptosis in the PBLs of patients with DTC. Therefore, it can be suggested that this method can be useful for monitoring and detecting destructive effects of ionizing radiation in nuclear medicine patients

Muc-1 Family Tumor Markers and Their Role in the Diagnosis of Breast Cancer, Review Article

Background & Objective: Tumor markers are elements produced by tumors or other cells in the body in response to cancer or some benign condition. Although most of these markers are made by normal cells as well as cancer cells, they are produced at much higher levels in cancerous conditions. This study aimed to provide a method for using tumor markers to diagnose cancer and detect the presence of metastasis and recurrence of the disease. Materials & Methods: The present narrative review study was done by selecting the appropriate keywords and searching for research and review studies indexed in Google Scholar, PubMed, Science Direct, and SID databases. Results: These studies often indicate the effective role of tumor markers in the MUC-1 family (especially Cancer antigen15-3(CA15-3)) and CEA (carcinoembryonic antigen) as the most widely used tumor markers in patients with breast cancer. Conclusions: Based on information from studies on tumor markers, the combination of CEA, CA15-3, PRL (prolactin), KL-6(Kerbs von den Lungen), Thioredoxin 1, and FER (ferritin) tumor markers can increase the sensitivity of early-stage breast cancer detection, and CA15-3 tumor markers can also be used to identify the presence or absence of metastasis to the axillary lymph nodes. The use of ultrasound (especially color Doppler) and its combination with CEA and CA15-3 tumor markers are recommended to improve the accuracy of a breast cancer diagnosis

Hesperidin as radioprotector against radiation-induced lung damage in rat: A histopathological study

Reactive oxygen species (ROS) are generated by ionizing radiation, and one of the organs commonly affected by ROS is the lung. Radiation-induced lung injury including pneumonia and lung fibrosis is a dose-limiting factor in radiotherapy (RT) of patients with thorax irradiation. Administration of antioxidants has been proved to protect against ROS. The present study was aimed to assess the protective effect of hesperidin (HES) against radiation-induced lung injury of male rats. Fifty rats were divided into three groups. G1: Received no HES and radiation (sham). G2: Underwent γ-irradiation to the thorax. G3: Received HES and underwent γ-irradiation. The rats were exposed to a single dose of 18 Gy using cobalt-60 unit and were administered HES (100 mg/kg) for 7 days before irradiation. Histopathological analysis was performed 24 h and 8 weeks after RT. Histopathological results in 24 h showed radiation-induced inflammation and presence of more inflammatory cells as compared to G1 (P < 0.05). Administration of HES significantly decreased such an effect when compared to G2 (P < 0.05). Histopathological evaluation in 8 weeks showed a significant increase in mast cells, inflammation, inflammatory cells, alveolar thickness, vascular thickness, pulmonary edema, and fibrosis in G2 when compared to G1 (P < 0.05). HES significantly decreased inflammatory response, fibrosis, and mast cells when compared to G2 (P < 0.05). Administration of HES resulted in decreased radiation pneumonitis and radiation fibrosis in the lung tissue. Thus, the present study showed HES to be an efficient radioprotector against radiation-induced damage in the lung of tissue rats