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Updated: May 15, 2026

Measuring DNA Damage and Repair in Mouse Splenocytes After Chronic In Vivo Exposure to Very Low Doses of Beta- and Gamma-Radiation
Published on: July 3, 2015
TGF-β signaling plays an important role in resisting γ-irradiation
You Sun An1, Mi-Ra Kim, Seung-Sook Lee
1Division of Radiation Effects, Korea Institute of Radiation and Medical Sciences, Seoul, Korea.
Abstract:
Transforming growth factor-β1 (TGF-β1) regulates various biological processes, including differentiation, bone remodeling and angiogenesis, and is particularly important as a regulator of homeostasis and cell growth in normal tissue. Interestingly, some studies have reported that TGF-β1 induces apoptosis through induction of specific genes, whereas others suggest that TGF-β1 inhibits apoptosis and facilitates cell survival. Resolving these discrepancies, which may reflect differences in cellular context, is an important research priority. Here, using the parental mink lung epithelial cell line, Mv1Lu, and its derivatives, R1B and DR26, lacking TGF-β receptors, we investigated the involvement of TGF-β signaling in the effects of γ-irradiation. We found that canonical TGF-β signaling played an important role in protecting cells from γ-irradiation. Introduction of functional TGF-β receptors or constitutively active Smads into R1B and DR26 cell lines reduced DNA fragmentation, Caspase-3 cleavage and γ-H2AX foci formation in γ-irradiated cells. Notably, we also found that de novo protein synthesis was required for the radio-resistant effects of TGF-β1. Our data thus indicate that TGF-β1 protected against γ-irradiation, decreasing DNA damage and reducing apoptosis, and thereby enhanced cell survival.
Insights
Transforming growth factor-β1 (TGF-β1) protects cells from gamma irradiation by reducing DNA damage and apoptosis. This signaling pathway enhances cell survival, clarifying its role in cellular response to radiation.
Area of Science:
- Cell Biology
- Molecular Biology
- Radiation Biology
Background:
- Transforming growth factor-β1 (TGF-β1) is a key regulator of cellular processes like differentiation, bone remodeling, and angiogenesis.
- TGF-β1's role in apoptosis is contradictory, with some studies showing induction and others inhibition, highlighting the need for context-specific investigation.
- Understanding TGF-β1's influence on cell survival and death is crucial for its role in homeostasis and growth.
Purpose of the Study:
- To investigate the role of TGF-β1 signaling in the cellular response to gamma irradiation.
- To resolve discrepancies regarding TGF-β1's effect on apoptosis in the context of radiation exposure.
- To elucidate the mechanisms by which TGF-β1 influences DNA damage and cell survival post-irradiation.
Main Methods:
- Utilized mink lung epithelial cell lines (Mv1Lu) and their TGF-β receptor-deficient derivatives (R1B, DR26).
- Assessed the impact of gamma irradiation on DNA fragmentation, Caspase-3 cleavage, and γ-H2AX foci formation.
- Investigated the requirement of de novo protein synthesis for TGF-β1's radio-protective effects.
Main Results:
- Canonical TGF-β1 signaling was found to be important in protecting cells against gamma irradiation.
- Restoration of TGF-β receptors or introduction of active Smads reduced DNA damage markers (fragmentation, γ-H2AX) and apoptosis (Caspase-3 cleavage) in irradiated cells.
- De novo protein synthesis was essential for TGF-β1 to confer radio-resistance.
Conclusions:
- TGF-β1 actively protects cells from gamma irradiation by mitigating DNA damage and suppressing apoptosis.
- The study clarifies TGF-β1's pro-survival role in response to radiation, enhancing overall cell survival.
- These findings emphasize the importance of TGF-β1 signaling in cellular radio-resistance and DNA repair mechanisms.
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