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Age and sex differences in genome damage between prepubertal and adult mice after exposureto ionising radiation.
Despite being an important diagnostic and treatment modality, ionizing radiation (IR) is also known to cause genotoxicity and multiple side effects leading to secondary carcinogenesis. While modern cancer radiation therapy has improved patient recovery and enhanced survival rates, the risk of radiation-related adverse effects has become a growing challenge. It is now well-accepted that IR-induced side effects are not exclusively restricted to exposed cells but also spread to distant ‘bystander’ cells and even to the unexposed progeny of the irradiated cells. These ‘off-targeted’ effects involve a plethora of molecular events depending on the type of radiation and tumor tissue background. While the mechanisms by which off-targeted effects arise remain obscure, emerging evidence based on the non-mendelian inheritance of various manifestations of them as well as their persistence for longer periods supports a contribution of epigenetic factors. This review focuses on the major epigenetic phenomena including DNA methylation, histone modifications, and small RNA mediated silencing and their versatile role in the manifestation of IR induced off-targeted effects. As short- and long-range communication vehicles respectively, the role of gap junctions and exosomes in spreading these epigenetic-alteration driven off-targeted effects is also discussed. Furthermore, this review emphasizes the possible therapeutic potentials of these epigenetic mechanisms and how beneficial outcomes could potentially be achieved by targeting various signaling molecules involved in these mechanisms.
The effect of nonylphenol (NP; either alone or in combination with ionizing radiation) on the induction of DNA strand breaks in mouse somatic cells has been examined. Male and female mice were repeatedly irradiated with X-rays (0.05 or 0.10 Gy), injected with NP (25 or 50 mg/kg bw), or both (0.05 Gy + 25 mg/kg bw NP or 0.10 Gy + 50 mg/kg bw NP), for 2 weeks, 5 days/week. Liver, spleen, femora, lungs and kidneys were removed from each animal for the comet assay. NP-induced DNA damage differed, depending on organ and sex. In male mice, NP induced damage in all organs examined; in females, only the kidneys were affected. The effect of irradiation alone was similar in females and males. Combined exposure of males to 0.05 Gy + 25 mg/kg bw NP significantly reduced the level of DNA strand breaks, compared to the controls and to 25 mg/kg bw NP alone, in the majority of organs. The higher doses significantly increased damage to DNA in all organs examined. Combined exposure of females to low doses of both agents significantly enhanced damage to DNA in bone marrow lymphocytes and in cells of the liver and kidneys, compared to controls. At 0.10 Gy + 50 mg/kg bw NP, DNA damage was increased in organs except liver and spleen. Although NP alone may not be mutagenic in female mice, its co-administration with irradiation may increase DNA damage in some organs. In contrast, in male mice, damage was reduced after combined irradiation-NP exposure, compared to NP alone.