| Project/Area Number |
61480307
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Cerebral neurosurgery
|
|---|
| Research Institution | Toyama Medical and Pharmaceutical University |
|---|
Principal Investigator |
PROF. TAKAKU Akira Department of Neurosurgery,School of Medicine,Toyama Medical and Pharmaceutical, 医学部, 教授 (70004984)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
ASSISTANT prof. OKA Nobu Department of Neurosurgery,School of Medicine,Toyama Medical and Pharmaceutical, 附属病院, 講師 (10135006)
堀江 幸男 富山医科薬科大学, 附属病院, 助手 (20135015)
|
|---|
| Project Period (FY) |
1986 – 1988
|
| Project Status |
Completed (Fiscal Year 1988)
|
| Budget Amount *help |
¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 1988: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1987: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1986: ¥2,700,000 (Direct Cost: ¥2,700,000)
|
|---|
| Keywords | ACNU / Chemotherapy / Drug resistance / Mutagenesis / 脳腫 / 突然変異 / 水溶性ニトロ 素系抗癌剤 / 脳腫瘍 / 悪性脳腫瘍 / 抗癌剤 / 突然変異原性 |
|---|
| Research Abstract |
The antitumor compound ACNU is widely used for treatment of malignant brain tumors. We have investigated the mechanism of acquisition of ACNU resistance at the cellular level by isolating ACNU-resistant mutants from V79 Chinese hamster cells and C6 rat glioma cells after treatment of the cells with ACNU or other alkylating agents. In V79 Chinese hamster cells, ACNU at 1 to 4 ug/ml caused dose-dependent induction of drug-resistant mutants to ACNU(10 ug/ml), 8-azaguanine(20 ug/ml), adriamycin(270 ng/ml),cisplation(1 ug/ml), mitomycin C(110 ng/ml) and demecolcin (21 ng/ml),but not to ouabain(1 mM).
Values for the mean lethal dose of ACNU-resistant mutants were 2.4 to 17.2 times those of the parent V79 cells. The ACNU-resistant phenotype was stable during an observation period of 13 weeks. The C6 rat glioma cells also showed a significant mutagenic response to ACNU, producing ACNU- and 5-fluorouracil-resistant mutants. The present results have the important therapeutic and mechanistic implication that ACNU is a potent mutagen and induces mutants that are resistant to ACNU and to other drugs. By addition of Ca2+- antagonist verapamil HCI to selection medium, mutants resistant to mitomycin C and adriamycin did not appear.
|
