Page 76 - ARNM-3-1

Advances in Radiotherapy
& Nuclear Medicine Aspirin’s protective effect on RISI

hand, the cycling cells were enriched in pathways related IFE B1 cells may represent a compensatory mechanism
to DNA repair, including “homologous recombination” aimed at maintaining epithelial integrity by promoting
and “non-homologous end joining” pathways, which are cell proliferation. ASP treatment appears to support
the primary repair mechanisms for DNA DSBs during this compensatory response by reducing the severity of
most of the cell cycle 25,26 . These findings suggest that IFE radiation-induced damage and enabling these cells to
C cells that successfully initiate DNA repair mechanisms proliferate and replace damaged tissue.
can progress through the cell cycle and contribute to tissue Our findings also raise important questions regarding
recovery. ASP appears to promote this process, possibly the long-term impact of ASP treatment in the context of
by modulating the activity of DNA repair pathways and radiation exposure. While ASP has demonstrated clear
5
reducing oxidative stress as well as helping DNA repair . benefits in reducing the severity of RISI in the short
The modified RISI scoring system based on the RTOG/ term, the potential effects on long-term skin health and
EORTC criteria proved to be highly effective for evaluating carcinogenesis require further exploration. The use of ASP
10
skin injury in this study. The scoring system allowed for in clinical settings has been associated with reduced risk
a nuanced assessment of RISI severity, capturing changes of certain cancers, and it will be important to determine
in erythema, dryness, desquamation, and necrosis at whether these protective effects extend to radiation-
various stages. The daily observation of mice and the induced carcinogenesis in skin tissue 27,29,30 . In addition,
detailed scoring system provided a robust dataset that understanding the precise molecular mechanisms through
highlighted differences in the temporal progression of RISI which ASP enhances DNA repair and modulates the
between ASP-treated and untreated groups. ASP-treated immune response will provide valuable insights into its
mice exhibited delayed onset and lower peak severity of potential applications in radiotherapy. Although scRNA-
RISI, underscoring the protective effects of ASP against seq of ASP-treated samples was not performed in this
radiation-induced damage. This refined scoring approach study due to resource limitations, such analyses could offer
could be highly valuable in future pre-clinical studies detailed insights into the molecular pathways modulated
investigating potential treatments for RISI. by ASP. Future studies should investigate this direction
to validate and expand upon the findings reported here.
ASP’s role in normal tissue protection and tumor Besides, the presence of tumors can significantly alter
radiosensitivity is distinct. While it facilitates DNA repair signaling pathways, potentially modifying the efficacy
in normal tissues, studies have shown its potential to of ASP in mitigating RISI. Investigating ASP’s effects in
enhance cancer cell radiosensitivity by downregulating tumor-bearing mouse models could provide clinically
COX-2 and inducing apoptosis . This dual mechanism relevant insights and enhance the translational potential
27
underlines its therapeutic potential in radiotherapy. ASP’s of our findings. This represents an important direction for
protective effects against RISI are likely multifaceted, future research.
involving modulation of both immune response and cell
cycle dynamics. Previous studies have shown that ASP 5. Conclusion
can act as a radiosensitizer in certain cancer types by Our study provides compelling evidence that ASP pre-
inhibiting key signaling pathways such as COX-2, which is treatment exerts a protective effect against RISI in a
involved in inflammation and tumor progression . In the mouse model. This protection is probably mediated
8,28
context of RISI, it is plausible that ASP’s anti-inflammatory through multiple mechanisms, including modulation of
properties help to mitigate the inflammatory response the immune response, enhancement of DNA repair, and
following radiation, thus reducing tissue damage and promotion of cell cycle re-entry in irradiated cells. These
improving overall skin health. Furthermore, our results findings suggest that ASP could be a promising adjunct
suggest that ASP may enhance the DNA repair capacity of therapy for mitigating the side effects of radiotherapy,
IFE C cells, thereby allowing them to overcome radiation- particularly in reducing skin toxicity. Future studies should
induced G2M arrest and re-enter the cell cycle, which is focus on elucidating the detailed molecular mechanisms
essential for tissue regeneration. underlying these protective effects and exploring the
The increased proportion of IFE B1 cells observed in potential of ASP in combination with other therapeutic
the irradiated group compared to the control group is agents to enhance skin recovery and reduce radiation-
an intriguing finding that warrants further investigation. related complications.
The IFE B1 cells are characterized by higher expression Acknowledgments
levels of Cdk1 and Ccnb1, indicating active cycling and
proliferation. Following irradiation, the enrichment of None.

Volume 3 Issue 1 (2025) 68 doi: 10.36922/arnm.5829