| Project/Area Number |
12836016
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Institution | Azabu University School of Veterinary Medicine |
|---|
Principal Investigator |
IKEDA Teruo Azabu University School of Veterinary Medicine, Associate Professor, 獣医学部, 助教授 (60151297)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KASHIWAZAKI Naomi Azabu University School of Veterinary Medicine, Associate Professor, 獣医学部, 助教授 (90298232)
INOMATA Tomoo Azabu University School of Veterinary Medicine, Associate Professor, 獣医学部, 助教授 (10147978)
SHIROTA Kinji Azabu University Research Institute Biosciences, Professor, 生物科学総合研究所, 教授 (70147974)
MORITA Hidetoshi Azabu University School of Veterinary Medicine, Associate Professor, 獣医学部, 助教授 (70257294)
|
|---|
| Project Period (FY) |
2000 – 2001
|
| Project Status |
Completed (Fiscal Year 2001)
|
| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2000: ¥2,400,000 (Direct Cost: ¥2,400,000)
|
|---|
| Keywords | P-glycoprotein / LLC-PK1 / Cloning / copulanar-PCB / drug transport / 薬物ポンプ / PCBs / MDR1 / KB-3 / P-glycoprotein / Drag transport / 多剤耐性遺伝子 / LLC-K1 / KB細胞 / 単層培養輸送系 / コルチゾール / エストラジオール |
|---|
| Research Abstract |
Endocrine disruptures such as sex-hormone like chmicals and the non-physiological ligands for aryl hydrocarbon and estrogen receptors involve many adverse biological reactions. Here we examined that transepithelial transport and cellular accumulation of cortisol and estrogen as congeners of sex-hormone like chemicals, and 3, 3', 4, 4' -tetrachlorobiphenyl(TeCB) as one of the isoforms of coplanar polychlorinated biphenyls(Co-PCBs), one of the ligand for Ahr, in a monolayer of porcine kidney cells(LLC-PK1) transfected with human P-glycoprotein(LLC-COL). Although the net basal-to-apical transport of cortisol increased in LLC-COL compared to that in LLC-PK1 as well as in vinblastine, the net transport of estradiol was not detected in either cells. Though the diffusion transports of estradiol in basal-to-apical and apical-basal were higherthan that of cortizol, cellular accumulation of estradiol was higher than that of cortizol. Transepothelial transport of TeCB was very low and the net bas
… More
al-apical transport was not detected, while it was highly accumulated in the epithelial cells. The accumulation was slightly higher thanin LLC-COL than in LLC-PK1 in high dose.
It was previously reported that the substitution of phenylalanin(F) for histidine-61(H61) in human P-glycopratein increase tolerance to smaller molecular drugs, and the substitution of serine(S) increase tolerance to large molecular drugs. Thus, the accumulation of vinblastine and colchicine, andTeCB was examined in human tumor cells, KB-3, expressing human P-glycoprotein (H61) and its mutants(F and S). The accumulation of vinblastine and colchicine was greatly decreased in transport cellsexpressing P-glycoprotein compared to wild type KB-3. However, the accumulation of TeCB did not differamong these cell groups. The deareases in drug accumulation in cells expressing P-glycoprotein were inhibited by adding verapamil, an inhibitor of P-glycoprotein, and decrease were also inhibited by adding TeCB. Thus, TeCB could be an inhibitor of P-glycoprotein and affect cell membrane drug transport.
Moreover we examined animal tumor cell lines isolated from dogs to detect MDR1 which be able to excrete copulanar PCBs. MDR1 gene for endobrine disruptures have not been isolated in our study. It seems that drug tranporter except for MDR such as ABC proteins should be examined for transport and accumulation of copulanar PCBs. Less
|
