Melatonin as an adjuvant in radiotherapy for radioprotection and radiosensitization.

It is estimated that more than half of cancer patients undergo radiotherapy during the course of their treatment. Despite its beneficial therapeutic effects on tumor cells, exposure to high doses of ionizing radiation (IR) is associated with several side effects. Although improvements in radiotherapy techniques and instruments could reduce these side effects, there are still important concerns for cancer patients. For several years, scientists have been trying to modulate tumor and normal tissue responses to IR, leading to an increase in therapeutic ratio. So far, several types of radioprotectors and radiosensitizers have been investigated in experimental studies. However, high toxicity of chemical sensitizers or possible tumor protection by radioprotectors creates a doubt for their clinical applications. On the other hand, the protective effects of these radioprotectors or sensitizer effects of radiosensitizers may limit some type of cancers. Hence, the development of some radioprotectors without any protective effect on tumor cells or low toxic radiosensitizers can help improve therapeutic ratio with less side effects. Melatonin as a natural body hormone is a potent antioxidant and anti-inflammatory agent that shows some anti-cancer properties. It is able to neutralize different types of free radicals produced by IR or pro-oxidant enzymes which are activated following exposure to IR and plays a key role in the protection of normal tissues. In addition, melatonin has shown the ability to inhibit long-term changes in inflammatory responses at different levels, thereby ameliorating late side effects of radiotherapy. Fortunately, in contrast to classic antioxidants, some in vitro studies have revealed that melatonin has a potent anti-tumor activity when used alongside irradiation. However, the mechanisms of its radiosensitive effect remain to be elucidated. Studies suggested that the activation of pro-apoptosis gene, such as p53, changes in the metabolism of tumor cells, suppression of DNA repair responses as well as changes in biosynthesis of estrogen in breast cancer cells are involved in this process. In this review, we describe the molecular mechanisms for radioprotection and radiosensitizer effects of melatonin. Furthermore, some other proposed mechanisms that may be involved are presented.

Comparison of the effects of Ham'sF10 and αMEM in combination with FBS or BSA in vitrification/warming solution on quality and viability of sheep ovarian follicles.

The aim of this study was to evaluate the effects of the two types of media, namely minimum essential medium (αMEM) and Ham'sF10, supplemented with foetal bovine serum (FBS) or bovine serum albumin (BSA) in vitrification/warming solution on the quality and viability of sheep ovarian follicles. Vitrification method was applied for cryopreservation of sheep ovarian cortex using Ham'sF10 and αMEM supplemented with either BSA or FBS. There were five groups: Fresh, Ham'sF10+ BSA, Ham'sF10+ FBS, αMEM + BSA and αMEM + FBS. Samples were cultured for two weeks after warming. Viability and morphology of follicles and DNA fragmentation in follicles and in tissue stroma cells were analysed before vitrification/warming and following one and two weeks of culture. The Ham'sF10+ FBS and Ham'sF10+ BSA groups showed a significant decrease in follicular viability after one week of culture (p < .05 vs. Fresh). Following two weeks of culture, all groups revealed a considerable fall in the number of viable follicles (p < .05 vs. Fresh). There was an increase in DNA fragmentation of connective tissue cells but not in the follicles (p < .05). Our results showed the better application of αMEM supplemented with BSA as a vitrification solution in improvement of cryopreservation effects and maintenance of follicular survival.