Investigation of molecular mechanism of radiosensitivity of the tumor cell and its clinical application

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1.We measured the activity of DNA-PK (DNA-dependent protein kinase) of two established cell lines that have the different radiosensitivity. One of them was HK-1 (malignant lymphoma) and the other was Suzuki(thyroid cancer). Suzuki is more radiosensitive than HK-1. However, there was no significant difference of the activity of DNA-PK between them.2.We made samll multicellular spheroids 100 mum in diameter with human osteosarcoma cell line (MG-63) to examine whether there was the difference of the activity of DNA-PK between monolayr and spheroid culture. MG-63 cells in spheroid culture become more radioresistant than monolayr culture. We used MG-63 cells of log phase and confluent phase of growth in monolayr culture as a control. However, there was no significant difference of the activity of DNA-PK in monolayr culture and spheroid culture.3.There are two processes of repair of potentially lethal damage following X irradiaiton ; a rapid repair process, which is completed in about 1 hour, is interrupted by hypertonic saline treatment, and a slower process, which requires several hours to be completed, is facilitated by the application of condititioned medium. As a medhanism of inhibition of a rapid repair process by hypertonic saline treatment, there was the possibility that hypertonic saline treatment might block the repair of DNA double strand break by inhibiting the activity of DNA-PK.Then, we used two types of malignant melanoma cell lines to check such possibility. G-361 cells (D_0=145cGy, Dq=249cGy) are more radioresistant and have the higher ability of a rapid repair process of PLD than P39 (D_0=74cGy, Dq=85cGy). However, in both cel lines, there was no significant difference of the activity of DNA-PK between groups with hypertonic saline treatment and those without treatment.