| Project/Area Number |
02670619
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Cerebral neurosurgery
|
|---|
| Research Institution | Hokkaido University |
|---|
Principal Investigator |
AIDA Toshimitsu Hokkaido University, School of Medicine, 医学部附属病院, 講師 (60125276)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SAWAMURA Yutaka Hokkaido University, School of Medicine, 医学部, 助手 (10235476)
TOKUDA Kouichi Hokkaido University, School of Medicine, 医学部, 助手 (00237067)
杉本 信志 北海道大学, 医学部, 助手 (60125325)
|
|---|
| Project Period (FY) |
1990 – 1991
|
| Project Status |
Completed (Fiscal Year 1991)
|
| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1991: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1990: ¥1,300,000 (Direct Cost: ¥1,300,000)
|
|---|
| Keywords | Brain tumor / Drug resistance / Anti-tumor drug / Chloroethyinitrosourea / ニトロソウレア系抗癌剤 / 抗癌剤耐性 |
|---|
| Research Abstract |
The purpose of this investigation was to determine the effect of pretreatment with 5-(3-methyl-l-triazeno)imidazole-4-carboxamide(MTIC)on cytotoxicity and induction of sister chromatid exchanges(SCEs)in a resistant human glioma cell line treated with 3-(4-amino-2-methyl-5-primidinyl)methyl-l-(2-chloroethyl)nitrosourea(ACNU), to overcome the cellular resistance to ACNU.
SF-188 and SF-126 are human glioma cell lines. SF-188 cells are very resistant to cytotoxic affects of ACNU. compared with SF-126 cells. Pretreatment with MTIC increased the cytotoxicityof ACNU in a dose dependent manner. Preteatment w i th 400 muM MTIC- potentiated ACNU cytotoxicity by 9-fol d and SF-1 88 cells became as sensitive as SF-126 cells. The potentiation of ACNU-induced SCEs by MTIC was also dose-dependent. The treatment of SF-188 cells with MTIC inhibited O^6-alkylguanine DNA alkyl-transferase(O^6-AT)activity.
These results shows that O^6-AT plays an important role in determining the cellular resistant to treatment with chloro-ethylnitrosourea(CENU)and that the reduction of O^6-AT activity in tumor cells which are resistant to CENUs may be used to improve the clinical effectiveness of CENUs.
Based on the results of this experiment, we designed a study of chemotherapy, with 5-(3, 3-dimethyl-l-triazeno)imidazole-4-carboxamide(DTIC), ACNU, vincristine for primary and recurrent malignant brain tumors.
|
