1998 Fiscal Year Final Research Report Summary
Evaluation of the antimutagenic effect of (-)-epegallocatechin gallate (EGCG) against chemical-induced mutagenesis of transgenic HITEC mice
| Project/Area Number |
09672206
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Kanazawa University |
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Principal Investigator |
YOKOI Tsuyoshi Faculty of Pharmaceutical Sciences, Kanazawa University, Professor, 薬学部, 教授 (70135226)
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| Co-Investigator(Kenkyū-buntansha) |
KAMATAKI Tetsuya Faculty of Pharmaceutical Sciences, Hokkaido University, Professor, 薬学部, 教授 (00009177)
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| Project Period (FY) |
1997 – 1998
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| Keywords | epigallocatechin gallate / benzo[a]pyrene / mutagenesis / antimutagenesis / HITEC mouse / rpsL gene / 遺伝子損傷 |
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| Research Abstract |
The antimutagenic activity of epegallocatechin gallate (EGCG), the major water soluble compound of green tea, against benzo[a]pyrene (B[a]P)-induced mutations were assessed by using transgenic mice carrying rpsL gene as a monitor of somatic mutations (HITEC mice). EGCG has been known to inhibit cytochrome P450. Male mice of 7 weeks old were given drinking water containing EGCG for 3 weeks. On day 7, mice were treated with a single i.p. injection of B[alpha]P (500 mg/kg bwt). Two weeks after the injection the mutaion of rpsL gene were analyzed. B[a]P treatment resulted in the significant approximately 4Ofold increase of mutation frequency in the lung of HITEC mice. Approximately 60% suppression of B[a]P-induced mutations in the lung was observed when mice were given EGCG at concentraions higher than 0.005% EGCG.B[alpha]P-induced mutations mainly occurred at G : C base-pairs. The majority of base substitutions were G : C*C : G transversions, followed by G : C*T : A transversions and G : C*A : T transitions. B[a]P-induced mutations frequently occurred in the several specific nucleotide sequences of the rpsL gene. These were AGC, CGC, CGT, TGC and CGT ; all of them contained guanine residue. B[a]P-induced mutaions seen in the mouse ras codon 12 or human p53 codon 157 were found in the rpsL gene, and that the mutations were suppressed by EGCG for B[alpha]P-induced mutagenesis in vivo suggest that the drinking of tea may reduce the tumor-initiating potency of B[a]P in the lung.
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Research Products
(19 results)
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[Publications] Ken-ichi Nunoya, Tsuyoshi Yokoi, Kanzo Kimura, Kazuaki Inoue, Takao Kodama, Masato Funayama, Kazuo Nagashima, Yoshihiko Funae, Carol E.Green, Moritoshi Kinoshita and Tetsuya Kamataki: "A new deleted allele in human cytochrome P450 2A6 gene (CYP2A6) causing poor capacity to metabolize (+)-cis-3,5-dimethyl-2(3-pyridyl)thiazolidin-4-one hydrochroride (SM-12502) in human liver microsomes." Pharmacogenetics. 8. 239-249 (1998)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Michihiro Chida, Tsuyoshi Yokoi, Yasuyuki Kosaka, Kan Chiba, Hidefumi Nakamura, Takashi Ishizaki, Jun Yokota, Moritoshi Kinoshita, Kunio Sato, Minoru Inaba, Yasuhiro Aoki, Frank J.Gonzalez and Tetsuya Kamataki: "Genetic polymorphism of CYP2D6 in Japanese population." Pharmacogenetics. (in press). (1999)
Description
「研究成果報告書概要(欧文)」より
