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

1997 Fiscal Year Final Research Report Summary

• Project/Area Number: 08671043
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Radiation science
• Research Institution: SAPPORO MEDICAL UNIVERSITY
• Principal Investigator: SAKATA Koh-ichi Sapporo medical university, Department of Radiology, Assistant Professor, 医学部, 講師 (10235153)
• Co-Investigator(Kenkyū-buntansha): MORITA Kazuo Sapporo medical university, Department of Radiology, Professor, 医学部, 教授 (20045347) ; HAREYAMA Masato Sapporo medical university, Department of Radiology, Associate Professor, 医学部, 助教授 (10173098)
• Project Period (FY): 1996 – 1997
• Keywords: DNA-PK / radiosensitivity / multicellular spheroids / potentially lethal damage

Research Abstract

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.