Head and neck cancer comprises malignant tumors affecting the oral cavity, pharynx, larynx, paranasal sinuses, and nasal cavity (National Cancer Institute, 2024). According to the World Health Organization, about two million people worldwide are expected to be diagnosed with head and neck cancer in 2025 (International Agency for Research on Cancer, 2024), with an estimated 700,000 deaths attributed to the disease in the same year (International Agency for Research on Cancer, 2024).

Radiation therapy is highly effective in achieving remission of head and neck tumors, regardless of tumor stage, and can be used alone or in combination with chemotherapy and surgery (Argiris et al., 2008). However, radiation therapy for head and neck cancer significantly impacts patients’ quality of life (Allal et al., 2000). Despite advancements in technology and new application protocols, radiation therapy-related side effects remain inevitable (Baudelet et al., 2019). Among these, structural damage to salivary glands impairs saliva production (Almståhl et al., 2015, Gaetti-Jardim et al., 2018, Müller et al., 2019), leading to xerostomia (Urek et al., 2005, Krishnan et al., 2017), alterations in salivary pH and buffering capacity, and a shift in the oral microbiota toward a more cariogenic profile. Consequently, patients are at increased risk of mucositis and radiation-induced caries (Sroussi et al., 2017).

Individuals undergoing radiation therapy in the head and neck region are expected to have an increased prevalence of apical periodontitis, as the rapid progression of radiation-induced caries exposes the root canal system to the oral environment (Hommez et al., 2012). Consequently, this process triggers pulpal changes that can lead to pulp necrosis and periapical pathology (Kakehashi et al., 1965). The prevalence of apical periodontitis appears to be related to the radiation dose (Hommez et al., 2012), and necrotic teeth in irradiated areas have been shown to harbor a more diverse and complex microbiota compared to non-irradiated teeth (Hommez et al., 2008), which may influence apical periodontitis progression. Furthermore, osteoclastogenesis in irradiated bone is compromised (Omar et al., 2024). The increase in pro-inflammatory cytokines in bone tissue subjected to radiation therapy promotes greater differentiation of osteoclastic cells while reducing osteoblast expression, contributing to impaired bone remodeling (Da Cruz Vegian et al., 2020). The onset and severity of these changes are dose-dependent (Bray et al., 2016). Radiation dosage is determined based on tumor size and location, and the individualization nature of treatment leads to variations in side effects. (Feng et al., 2021).

Although radiation therapy is known to induce significant changes in oral tissues, its specific impact on the progression of apical periodontitis remains underexplored (Nagler, 2001; Cihan et al., 2013; Elsaadany et al., 2019; Hsieh et al., 2013). Moreover, no study has systematically assessed whether different radiation doses influence the progression of apical periodontitis. Given that radiation exposure may compromise the host response, it is plausible that varying radiation doses could differentially affect apical periodontitis development and severity. However, this hypothesis has not been investigated. Therefore, this study aims to evaluate the effect of different radiation therapy doses on the progression of apical periodontitis in rats. By addressing this gap, our findings may contribute to a better understanding of the relationship between radiation exposure and periapical disease, providing insights that could help guide clinical management strategies for irradiated patients. The null hypothesis tested is that radiation therapy, regardless of the dose, does not influence the progression of apical periodontitis.