Abstract
The prognosis and treatment of thyroid cancer depends on the type and stage of the disease. Radiosensitivity differs among cancer cells owing to their varying capacity for repair after irradiation. Radioactive iodine can be used to destroy thyroid cancer cells. However, patient prognosis and improvement after irradiation varies. Therefore, predictive measures are important for avoiding unnecessary exposure to radiation. We describe a new method for predicting the effects of radiation in individual cases of thyroid cancer based on the DNA-dependent protein kinase (DNA-PK) activity level in cancer cells. The radiation sensitivity, DNA-PK activity, and cellular levels of DNA-PK complex subunits in five human thyroid cancer cell lines were analyzed in vitro. A positive correlation was observed between the D10 value (radiation dose that led to 10% survival) of cells and DNA-PK activity. This correlation was not observed after treatment with NU7441, a DNA-PK–specific inhibitor. A significant correlation was also observed between DNA-PK activity and expression levels of the DNA-PK catalytic subunit (DNA-PKcs). Cells expressing low DNA-PKcs levels were radiation-sensitive, and cells expressing high DNA-PKcs levels were radiation-resistant. Our results indicate that radiosensitivity depends on the expression level of DNA-PKcs in thyroid cancer cell lines. Thus, the DNA-PKcs expression level is a potential predictive marker of the success of radiation therapy for thyroid tumors.
Highlights
DNA double-stranded breaks (DSBs) are a highly cytotoxic form of DNA damage induced by ionizing radiation [1, 2]
Thyroid cancer cells were separated into the three groups of radioresistant, moderately radiosensitive, and radiosensitive groups based on the dose that led to 10% survival (D10) values
The enhancement ratio (D10 of non-treated cells/D10 of NU7441-treated cells) of TPC-1, KTC-1, WRO and KTC-2 was >6. This indicates that NU7441 treatment induces 6-fold greater radiation sensitivity in these cells. This suggests that the major DSB repair mechanism in these cells is the NU7441-sensitive DNA-PK–mediated repair mechanism (NHEJ)
Summary
DNA double-stranded breaks (DSBs) are a highly cytotoxic form of DNA damage induced by ionizing radiation [1, 2]. If repaired incorrectly, DSBs induce mutations, chromosomal aberrations, and cell death. DSBs are repaired mainly by homologous recombination (HR) or non-homologous end joining (NHEJ) [3, 4]. Double-strand DNA–dependent protein kinase (DNAPK) plays an important role in NHEJ. DNA-PK is a serine/threonine protein kinase, composed of a DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and a Ku70/80 heterodimer.
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