Establishment of a Precise Mouse Model of Radiation Proctitis Using Localized Rectal Irradiation

Aim: To establish a reproducible and anatomically precise mouse model of radiation proctitis (RP) using localized rectal irradiation, and to determine the optimal radiation dose that balances pathological fidelity and animal survival, providing a robust platform for mechanistic studies and therapeutic evaluation.

Methods: Eight-week-old male C57BL/6 mice were anesthetized and subjected to single-fraction localized rectal irradiation using a 6 MV X-ray linear accelerator. A defined rectal field (1 × 2 cm) was precisely positioned to target the rectum while sparing surrounding tissues. Mice were assigned to different dose groups (0, 10, 20, 40, 50, and 60 Gy; n = 12 per group). Rectal tissues were harvested at 7, 14, 21, and 28 days post-irradiation for histopathological evaluation using hematoxylin and eosin staining. Tissue injury severity, inflammatory infiltration, structural integrity, and animal survival were systematically assessed.

Results: Localized rectal irradiation successfully induced dose-dependent radiation-induced rectal injury. Low-dose groups (10–20 Gy) exhibited minimal or mild mucosal damage, with no significant mortality. High-dose irradiation (50–60 Gy) caused extensive transmural injury with loss of normal rectal architecture, accompanied by marked inflammatory cell infiltration and high mortality rates (50 Gy: 50% mortality within 14 days; 60 Gy: >90% mortality within 14 days). In contrast, the 40 Gy group demonstrated consistent and reproducible rectal injury, characterized by moderate-to-severe mucosal and submucosal damage, uniform pathological features, and low mortality (8% within 28 days). Partial tissue recovery was observed at 28 days post-irradiation, enabling longitudinal observation and interventional studies.

Conclusion: A localized rectal irradiation dose of 40 Gy reliably establishes a stable and reproducible mouse model of radiation proctitis with acceptable survival. This model closely mimics clinical radiation-induced rectal injury and provides a practical, translationally relevant platform for studying RP pathogenesis and evaluating therapeutic strategies.