Radioprotective Effects of Combined Melatonin and Famotidine Treatment on Radiation Induced Apoptosis in Peripheral Blood Leukocytes of Breast Cancer Patients and Normal Individuals

Abstract

Objective: The aim of this study was to evaluate the effects of individual or combined use of two antioxidants, melatonin and famotidine on radiation induced apoptosis in leukocytes from breast cancer (BC) patients. Materials and Methods: In this experimental study, the DPPH assay was used to determine the appropriate doses of melatonin and famotidine for treatment of BC and control leukocytes. The leukocytes were cultured in complete RPMI- 1640 medium and treated with either agent for two hours. Cells were exposed to 4 Gy gamma rays generated from a Co-60 source at a dose rate of 0.85 Gy for 48 hours before harvesting. The cells were placed on slides and the neutral comet assay was performed. A total of 500 cells were stained with ethidium bromide and assessed for the amount of apoptosis under a fluorescent microscope x400 magnification. Results: We observed significantly more apoptosis following radiation alone in the leukocytes from BC patients compared with normal individuals (P0.05). However, when combined with radiation, there was a decreased frequency of apoptosis in leukocytes of both normal and BC patients (P<0.05). The effect of famotidine was more pronounced than melatonin. Conclusion: Melatonin, despite its potent antioxidant property, does not significantly affect radiation induced apoptosis in leukocytes derived from normal individuals; however, it has a moderately significant protective effect on in leukocytes derived from BC patients. Therefore, when used with radiation it might not intervene with the radiotherapy (RT) regimen of BC cancer patients. Famotidine is a good radioprotector for normal tissue. However, the efficacy of RT might be reduced with an accumulation of famotidine in tumour tissues.

Keywords

• antioxidants
• apoptosis
• breast cancer
• ionizing radiation
• leukocytes