| Project/Area Number |
05557120
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | Keio University |
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Principal Investigator |
KATO Ryuichi Keio Univ., Sch.of Med., Professor, 医学部, 教授 (40112685)
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| Co-Investigator(Kenkyū-buntansha) |
FUJITA Masataka Meiji Seika Kaisha, LTD,Pharmaceutical Research Center, Director, 薬品総合研究所・安全性研究所, 所長
YASUMORI Toshio Keio Univ., Sch.of Med., Assistant, 医学部, 助手 (70182350)
NAGATA Kiyoshi Tohoku Univ., Fac.of Pharm.Sci., Assistant, 薬学部, 助手 (80189133)
OZAWA Shogo Keio Univ., Sch.of Med., Assistant, 医学部, 助手 (20185581)
YAMAZOE Yasushi Tohoku Univ., Fac.of Pharm.Sci., Professor, 薬学部, 教授 (00112699)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥15,400,000 (Direct Cost: ¥15,400,000)
Fiscal Year 1994: ¥5,300,000 (Direct Cost: ¥5,300,000)
Fiscal Year 1993: ¥10,100,000 (Direct Cost: ¥10,100,000)
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| Keywords | Ames test / Mutagenicity / Carcinogenicity / Drug metabolizing enzymes / Metabolic activation / Acetyltransferase / Sulfotransferase / Gene expression / Anes試験 / アセチル化酵素 / アセチル化酵素遺伝子 / 異所遺伝子発現 / アリルアミン / N,O‐アセチル転移反応 / サルモネラ菌 / ベンチジン |
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| Research Abstract |
We have been studying metabolic activation of carcinogenic arylamines in mammalian livers and Salmonella. We reported that N,O-acetyltransferase and sulfotransferase, which playd a role in the metabolic activation in mammalian livers, were deficient in Ames tester strains. In this project, we newly established two Ames tester strains in which hamster arylamine acetyltransferase and rat N-hydroxy arylamine O-sulfotransferase were independently expressed. The new strains were 100-10,000times more sensitive to environmental carcinogens including N-hydroxy-2-acetylaminofluorene. Furthermore, the acetyltransferase-expressing strain showed high sensitivity to benzidine to which no Ames tester strain had showed any sensitivity.
The acetyltransferase and the sulfotransferase were shown to catalyze activation of N-hydroxy derivatives of not only arylamine (amide) s but also food-derived pyrolysate carcinogens.
These results indicated that the expression of mammalian esterification enzymes in Salmonella Ames tester strain resulted in new highly sensitive tester strains toward various kinds of environmental carcinogens. Thus, we concluded that this kind of approach is useful for the more predictive assessment of environmental mutagens and carcinogens.
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