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Low-Dose Caffeine Exposure Protects the Human Genome from Ionizing Radiation-Induced Damage and Prolongs Mouse
Susmita Kumari1, Supriya V Vartak1, Sabita Tamang1
1Department of Biochemistry, Indian Institute of Science, Bangalore, India.
Molecular and Cellular Biology
|November 13, 2025
Summary
Caffeine, found in coffee, protects against ionizing radiation (IR) damage by reducing DNA breaks and reactive oxygen species (ROS). This radioprotective effect enhances survival in mice, highlighting caffeine
Area of Science:
- Biochemistry
- Molecular Biology
- Radiation Biology
Background:
- Coffee is a globally consumed beverage, with caffeine being its primary active methylxanthine compound.
- Ionizing radiation (IR) poses significant health risks due to DNA damage and cellular stress.
- Understanding radioprotective agents is crucial for mitigating radiation-induced harm.
Purpose of the Study:
- To investigate the potential radioprotective effects of caffeine against ionizing radiation.
- To elucidate the molecular mechanisms underlying caffeine's interaction with radiation-induced DNA damage and cellular responses.
- To evaluate caffeine's efficacy in enhancing survival rates in a preclinical model post-irradiation.
Main Methods:
- In vitro studies exposing naked plasmid DNA and oligomeric DNA to IR in the presence and absence of caffeine.
- Cellular assays assessing DNA breaks and G2/M arrest in human cells exposed to IR with or without caffeine.
- In vivo studies using NOS2 knockout (KO) and wild-type (WT) mice, evaluating survival rates post-IR after caffeine treatment.
- Transcriptome analysis to identify gene expression changes related to antioxidant pathways.
Main Results:
- Caffeine significantly reduced IR-induced DNA breaks in both cell-free DNA and human cells, with minimal G2/M arrest.
- Caffeine demonstrated radioprotection by quenching reactive oxygen species (ROS).
- Caffeine treatment led to significantly enhanced survival in NOS2 KO mice compared to WT mice post-IR.
- Transcriptome analysis revealed upregulation of key antioxidant genes (e.g., Gpx3, Gpx7, Gpx4, Idh1) in caffeine-treated mice, particularly in NOS2 KO mice.
Conclusions:
- Caffeine exhibits significant radioprotective properties against ionizing radiation.
- The mechanism involves ROS quenching and upregulation of endogenous antioxidant defense systems.
- Caffeine holds potential as a radioprotective agent, mitigating radiation-induced damage and improving survival outcomes.
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