Melatonin, the chief secretary product of pineal gland, is a strong free radical scavenger and antioxidant molecule. The radioprotective efficacy and underlying mechanisms refer to its antioxidant role in somatic cells. The purpose of this study, therefore, was to investigate the prophylactic implications of melatonin against γ-ray-induced injury in germinal cells (testes). C57BL/6 male mice were administered melatonin (100 mg/kg) intra-peritoneally 30 min prior to a single dose of whole-body γ-irradiation (5 Gy, 1 Gy/minute) using 60Co teletherapy unit. Animals were sacrificed at 2h, 4h and 8h post-irradiation and their testes along with its spermatozoa taken out and used for total antioxidant capacity (TAC), lipid peroxidation, comet assay, western blotting and sperm motility and viability. In another set of experiment, animals were similarly treated were sacrificed on 1st, 3rd, 7th, 15th and 30th day post-irradiation and evaluated for sperm abnormalities and histopathological analysis. Whole-body γ-radiation exposure (5 Gy) drastically depleted the populations of spermatogenic cells in seminiferous tubules on day three, which were significantly protected by melatonin. In addition, radiation-induced sperm abnormalities, motility and viability in cauda-epididymes were significantly reduced by melatonin. Melatonin pre-treatment significantly inhibited radiation-induced DNA strands breaks and lipid peroxidation. At this time, radiation-induces activation of ATM-dependent p53 apoptotic proteins-ATM, p53, p21, Bax, cytochrome C, active caspase-3 and caspases-9 expression, which were significantly reversed in melatonin pre-treated mice. This reduced apoptotic proteins by melatonin pre-treatment was associated with the increase of anti-apoptotic-Bcl-x and DNA repair-PCNA proteins in irradiated mice. Further, radiation-induced decline in the TAC was significantly reversed in melatonin pre-treated mice. The present results indicated that melatonin as prophylactic agent protected male reproductive system against radiation-induced injury in mice. The detailed study will benefit in understanding the role of melatonin in modulation of radiation-induced ATM-dependent p53-mediated pro-vs.-anti apoptotic proteins in testicular injury. These results can be further exploited for use of melatonin for protection of male reproductive system in radiotherapy applications involving hemibody abdominal exposures.

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Ionising radiation causes free radical–mediated damage in cellular DNA. This damage is manifested as chromosomal aberrations and micronuclei (MN) in proliferating cells. Sesamol, present in sesame seeds, has the potential to scavenge free radicals; therefore, it can reduce radiation-induced cytogenetic damage in cells. The aim of this study was to investigate the radioprotective potential of sesamol in bone marrow cells of mice and related haematopoietic system against radiation-induced genotoxicity. A comparative study with melatonin was designed for assessing the radioprotective potential of sesamol. C57BL/6 mice were administered intraperitoneally with either sesamol or melatonin (10 and 20mg/kg body weight) 30min prior to 2-Gy whole-body irradiation (WBI) and sacrificed after 24h. Total chromosomal aberrations (TCA), MN and cell cycle analyses were performed using bone marrow cells. The comet assay was performed on bone marrow cells, splenocytes and lymphocytes. Blood was drawn to study haematological parameters. Prophylactic doses of sesamol (10 and 20mg/kg) in irradiated mice reduced TCA and micronucleated polychromatic erythrocyte frequency in bone marrow cells by 57% and 50%, respectively, in comparison with radiation-only groups. Sesamol-reduced radiation-induced apoptosis and facilitated cell proliferation. In the comet assay, sesamol (20mg/kg) treatment reduced radiation-induced comets (% DNA in tail) compared with radiation only (P < 0.05). Sesamol also increased granulocyte populations in peripheral blood similar to melatonin. Overall, the radioprotective efficacy of sesamol was found to be similar to that of melatonin. Sesamol treatment also showed recovery of relative spleen weight at 24h of WBI. The results strongly suggest the radioprotective efficacy of sesamol in the haematopoietic system of mice.

Protection of γ-ray-induced injury in hematopoietic and gastrointestinal (GI) systems is the rationale behind developing radioprotectors. The objective of this study, therefore, was to investigate the radioprotective efficacy and mechanisms underlying sesamol in amelioration of γ-ray-induced hematopoietic and GI injury in mice. C57BL/6 male mice were pre-treated with a single dose (100 or 50 mg/kg, 30 min prior) of sesamol through the intraperitoneal route and exposed to LD_50/30 (7.5 Gy) and sublethal (5 Gy) dose of γ-radiation. Thirty-day survival against 7.5 Gy was monitored. Sesamol (100 mg/kg) pre-treatment reduced radiation-induced mortality and resulted survival of about 100% against 7.5 Gy of γ-irradiation. Whole-body irradiation drastically depleted hematopoietic progenitor stem cells in bone marrow, B cells, T cell subpopulations, and splenocyte proliferation in the spleen on day 4, which were significantly protected in sesamol pre-treated mice. This was associated with a decrease of radiation-induced micronuclei (MN) and apoptosis in bone marrow and spleen, respectively. Sesamol pre-treatment inhibited lipid peroxidation, translocation of gut bacteria to spleen, liver, and kidney, and enhanced regeneration of crypt cells in the GI system. In addition, sesamol pre-treatment reduced the radiation-induced pattern of expression of p53 and Bax apoptotic proteins in the bone marrow, spleen, and GI. This reduction in apoptotic proteins was associated with the increased anti-apoptotic-Bcl-x and PCNA proteins. Further, assessment of antioxidant capacity using ABTS and DPPH assays revealed that sesamol treatment alleviated total antioxidant capacity in spleen and GI tissue. In conclusion, the results of the present study suggested that sesamol as a single prophylactic dose protects hematopoietic and GI systems against γ-radiation-induced injury in mice.

Ionizing radiation exposure is harmful and at high doses can lead to acute hematopoietic radiation syndrome. Therefore, agents that can protect hematopoietic system are important for development of radioprotector. Sesamol is a potential molecule for development of radioprotector due to its strong free radical scavenging and antioxidant properties. In the present study, sesamol was evaluated for its role in DNA damage and repair in hematopoietic system of γ‐irradiated CB57BL/6 mice and compared with amifostine. C57BL/6 male mice were administered with sesamol 20 mg/kg (i.p.) followed by 2 Gy whole body irradiation (WBI) at 30 min. Mice were sacrificed at 0.5, 3, 24 h postirradiation; bone marrow, splenocytes, and peripheral blood lymphocytes were isolated to measure DNA damages and repair using alkaline comet,γ‐H2AXand micronucleus assays. An increase in % of tail DNA was observed in all organs of WBI mice. Whereas in pre‐administered sesamol reduced %DNA in tail (P ≤ 0.05). Sesamol has also reduced formation of radiation induced γ‐H2AX foci after 0.5 h in these organs and further lowered to respective control values at 24 h of WBI. Similar reduction of % DNA in tail and γ‐H2AX foci were observed with amifostine (P ≤ 0.05). Analysis of mnPCE frequency at 24 h has revealed similar extent of protection by sesamol and amifostine. Interestingly, both sesamol and amifostine, alone and with radiation, also increased the granulocytes count significantly compared to the control (P ≤ 0.05). These findings suggest that sesamol has strong potential to protect hematopoietic system by lowering radiation induced DNA damages and can prevent acute hematopoietic syndrome in mice. Environ. Mol. Mutagen. 59:79–90, 2018.

Exposure to ionizing radiations, whether medical, occupational or accidental, leads to deleterious biological consequences like mortality or carcinogenesis. It is considered that no dose of ionizing radiation exposure is safe. However, once the accurate absorbed dose is estimated, one can be given appropriate medical care and the severe consequences can be minimized. Though several accurate physical dose estimation modalities exist, it is essential to estimate the absorbed dose in biological system taking into account the individual variation in radiation response, so as to plan suitable medical care. Over the last several decades, lots of efforts have been taken to design a rapid and easy biological dosimeter requiring minimum invasive procedures. The metaphase chromosomal aberration assay in human lymphocytes, though is labor intensive and requires skilled individuals, still remains the gold standard for radiation biodosimetry. The current review aims at discussing the human lymphocyte metaphase chromosomal aberration assay and recent developments involving the application of molecular cytogenetic approaches and other technological advancements to make the assay more authentic and simple to use even in the events of mass radiation casualties.