Abstract
BackgroundGenomic 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.ObjectiveIn this study, mice were exposed to whole-body gamma (γ)-irradiation to evaluate the specific DDR of various tissues. We treated male C57BL6/J mice with γ-irradiation at different doses, and the DDR protein levels in different tissues were analyzed.ResultsThe level of gamma-H2A histone family member X (γH2AX) increased in most organs after exposure to γ-irradiation. In particular, the liver, lung, and kidney tissues showed higher γH2AX 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 γ-irradiation.ConclusionThese results suggest that each tissue has a preferable repair mechanism in response to γ-irradiation. Therefore, the understanding and application of tissue-specific DNA damage responses could improve the clinical approach of radiotherapy for treating specific cancers.
Highlights
In mammals, including humans, the genome is continuously damaged by exogenous or endogenous factors during various biological processes such as replication and transcription
We found that various tissues differentially responded to whole-body γ-irradiation (WBI) in a mouse model
Our study provides a rationale for the appropriate application of radiotherapy and improves the knowledge on the tissue specificity of DNA damage response (DDR) at the organism level
Summary
In mammals, including humans, the genome is continuously damaged by exogenous or endogenous factors during various biological processes such as replication and transcription. This could result in genomic instability if not repaired. The loss of genomic stability due to exposure to DNA-damaging agents can trigger the development of various types of cancers and cell death. 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 γ-irradiation. Conclusion These results suggest that each tissue has a preferable repair mechanism in response to γ-irradiation. The understanding and application of tissue-specific DNA damage responses could improve the clinical approach of radiotherapy for treating specific cancers
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