Tissue-specific DNA damage response in Mouse Whole-body irradiation

Abstract

Background Genomic instability is a hallmark of various cancers, and DNA repair is an essential process for maintaining genomic integrity. Mammalian cells have developed various DNA repair mechanisms in response to DNA damage. Compared to the cellular response to DNA damage, the in vivo DNA damage response (DDR) of specific tissues has not been studied extensively. Objective In this study, mice were exposed to whole-body gamma (gamma)-irradiation to evaluate the specific DDR of various tissues. We treated male C57BL6/J mice with gamma-irradiation at different doses, and the DDR protein levels in different tissues were analyzed. Results The level of gamma-H2A histone family member X (gamma H2AX) increased in most organs after exposure to gamma-irradiation. In particular, the liver, lung, and kidney tissues showed higher gamma H2AX induction upon DNA damage, compared to that in the brain, muscle, and testis tissues. RAD51 was highly expressed in the testis, irrespective of irradiation. The levels of proliferating cell nuclear antigen (PCNA) and ubiquitinated PCNA increased in lung tissues upon irradiation, suggesting that the post-replication repair may mainly operate in the lungs in response to gamma-irradiation. Conclusion These results suggest that each tissue has a preferable repair mechanism in response to gamma-irradiation. Therefore, the understanding and application of tissue-specific DNA damage responses could improve the clinical approach of radiotherapy for treating specific cancers.