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Report No.

Investigation of radioresistant mechanisms in oral squamous cell carcinoma cells in in hypoxic environment

Tosa, Nanami*; Saga, Ryo*; Matsuya, Yusuke  ; Hosokawa, Yoichiro*

Cancer cells exposed to a hypoxic environment show malignant progression such resistant to both chemotherapy and radiotherapy. During fractionated radiotherapy (e.g., 2 Gy/fraction), due to broken fragile blood vessels, cancer cells near blood vessels are exposed to a hypoxic environment, leading to cancer stem-like cells (CSCs) niches and reduced radiosensitivity. However, the radioresistant mechanisms of cancer cells in hypoxia remain uncertain. In this study, we investigated the relationship between CSC fraction and radioresistance in hypoxia. The experimental results on surviving fraction of oral squamous cell carcinoma cells (HSC3 cells) shows that the radiosensitivity can be reduced as exposure time of hypoxia becomes longer. Meanwhile, using the integrated cell-killing model explicitly considering oxygen effects and CSC population (so called integrated microdosimetric-kinetic (IMK) model), the reduced radiosensitivity could be reproduced by reduced DNA damage yield and increased CSC fraction due to lack of oxygen. This work would contribute to the radioresistant mechanisms and the precise understanding of the therapeutic effects during fractionated radiotherapy.



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