Iodine 125 (125 I) seed irradiation is an effective non-surgical treatment for unresectable hepatocellular carcinoma (HCC) patients. However, the safety and tolerability of 125 I seed sequential irradiation therapy remain unclear, there is no unified standard of brachytherapy radiation dose, and further study on the basic radiobiology of continuous rate irradiation is necessary. Methods: Forty Kunming-mice (KM-mice, China) were injected with suspensions of human hepatocellular carcinoma cells

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... 22) to create an animal model and mimic 125 I seed implantation. The survival rates of mice, curative effect, pathological impairments including apoptosis and necrosis were investigated. The mice were randomly divided into four groups, A, B, C and D. In group A, 0.78 mCi 125 I seeds were implanted into the tumor focus. In groups B and C, 0.58 mCi and 0.38 mCi 125 I seeds were inserted at the same location, respectively. Group D was a control group, without any treatment. After 28 days of therapy, the survival rates and the tumor size were measured, and pathological impairments was measured by light or electron microscopy. Results: The tumor volume inhibition rate was 68.21% ± 3.21%, 51.38% ± 4.96%, and 35.71% ± 2.79% after 0.78 mCi, 0.58 mCi, and 0.38 mCi 125 I seeds irradiation, respectively. However, radiation-related side effects were also observed in the high-dose group. Pathological results showed that radiation effect was closely associated with radiation dose, as the increase of radiation dose, an increase in apoptosis and necrosis was detected. Significant cellular impairments were noted by pathological analysis under electron microscopy. Conclusions: Our results demonstrate that the Kunming-mouse is an ideal animal to study 125 I brachytherapy, and the curative effect was closely associated with radiation dose. High-dose of brachytherapy may effectively increase apoptosis and ne-crosis in liver cells in KM-mice. A dose of 0.58 mCi 125 I radioactive particles may be a safe, effective and minimally invasive therapeutic option for liver cancer.