Page 66 - ARNM-3-1

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

inflammation, desquamation, ulceration, and in severe the homologous recombination pathway is crucial for
cases, necrosis and fibrosis, all of which significantly maintaining genomic stability in the face of radiation
reduce the quality of life for patients undergoing radiation damage . ASP’s ability to facilitate this pathway may thus
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therapy . enhance cellular resilience to radiation, particularly in
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The pathophysiology of RISI involves complex interfollicular epidermal (IFE) cells, which are essential for
interactions between radiation-induced DNA damage, maintaining skin integrity and healing after injury.
inflammation, and impaired wound healing. Ionizing Previous studies have demonstrated that ASP exhibits a
radiation leads to the generation of reactive oxygen dual mechanism: Reducing inflammation and promoting
species, causing extensive damage to cellular structures, DNA repair in normal tissues while sensitizing cancer
particularly DNA. Double-strand breaks (DSBs) are the cells to radiotherapy through cyclooxygenase-2 (COX-2)
most lethal form of DNA damage caused by radiation, pathway inhibition. These effects make ASP a promising
and inefficient repair of these lesions results in cell death adjunctive therapy for radiotherapy .
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or senescence. In addition, radiation disrupts the balance The objective of this study was to investigate the
of cytokines, resulting in an inflammatory cascade that preventive and protective effects of ASP in a mouse model
further exacerbates tissue injury and delays the healing of RISI and to elucidate its potential mechanisms of
process . These challenges highlight the need for action. We hypothesized that ASP could play a key role in
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innovative therapies that not only address the symptoms of mitigating the severity of RISI by promoting DNA repair in
RISI but also target the underlying mechanisms of injury. IFE cells, thereby enhancing cellular resilience to radiation-
Current treatments for RISI remain largely inadequate, induced damage. By advancing our understanding of ASP’s
often failing to significantly alleviate the symptoms or protective mechanisms, this study aims to contribute to the
reverse the damage caused by radiation. Standard care, development of more effective strategies to protect patients
which includes the use of corticosteroids, non-steroidal from the adverse effects of radiation therapy.
anti-inflammatory drugs, and advanced wound dressings,
primarily focuses on managing symptoms rather than 2. Materials and methods
preventing the occurrence or progression of injury. These 2.1. RISI mouse model
interventions provide limited benefit, particularly for To establish the RISI model, we used 8 – 12-week-old
severe cases, and do not effectively target the underlying female C57BL/6 mice (Guangdong Medical Laboratory
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DNA damage or inflammation that drives RISI . The lack Animal Center, China). Mice were maintained in a
of effective preventative measures to protect the skin from controlled animal facility under specific pathogen-free
radiation underscores the importance of identifying novel conditions, with a temperature of approximately 23°C in a
agents that can mitigate radiation-induced cellular damage 12-h light/dark cycle. The mice received sterile commercial
and enhance the skin’s innate repair mechanisms.
rodent chow and water ad libitum. For the RISI model, the
Recent research has suggested that aspirin (ASP), a proximal right hind limb was shaved to expose the thigh
non-steroidal anti-inflammatory drug, can help mitigate skin. The mice were anesthetized using chloral hydrate
radiation-induced genotoxic effects through its ability to and properly immobilized. Radiation was delivered using
promote DNA repair. Specifically, ASP has been found a Varian linear accelerator (6 MV, 3 Gy/min) to administer
to enhance homologous recombination, facilitating the a single dose of 20 Gy X-ray irradiation to the thigh skin.
repair of radiation-induced DSBs in DNA, which are a Control mice underwent the same procedures, including
major contributor to cell damage and death following shaving, anesthesia, and immobilization, but were not
radiation exposure . ASP has also been reported to inhibit irradiated .
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the activity of pro-inflammatory pathways, which play a
critical role in the inflammatory response to radiation . By 2.2. RISI scoring system
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both promoting DNA repair and reducing inflammation, The severity of RISI was assessed using a modified scoring
ASP may offer a multifaceted protective effect against RISI. system based on the Radiation Therapy Oncology Group/
This dual mechanism makes ASP an attractive candidate European Organization for Research and Treatment of
for further investigation as a prophylactic treatment for Cancer (RTOG/EORTC) grading criteria . This modified
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patients undergoing radiotherapy. ASP’s role in DNA system allows for a more detailed and statistically
repair and inflammation modulation suggests that it appropriate assessment of RISI severity, with scores ranging
could be particularly beneficial in the context of RISI, from 1 to 5.5. The detailed scoring system used in this
where both genotoxic stress and inflammation play key study is shown in Table 1, which includes categories from
roles. Furthermore, previous studies have shown that normal skin (score = 1.0) to severe injury (score = 5.5),

Volume 3 Issue 1 (2025) 58 doi: 10.36922/arnm.5829