2007 Fiscal Year Final Research Report Summary
Relationship between xenobiotic toxicity and metabolisn in individuals
Project/Area Number |
18590116
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Environmental pharmacy
|
Research Institution | Okayama University |
Principal Investigator |
HANIOKA Nobumitsu Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Associate Professor (70228518)
|
Co-Investigator(Kenkyū-buntansha) |
NARIMATSU Shizuo Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Professor (20113037)
|
Project Period (FY) |
2006 – 2007
|
Keywords | Environmental pollutants / Drug-metabolizing enzymes / UDP-glucuronosyltransferase / β-nanhthoflavone / HepG2 cells / UGT1A1 / UGT1A6 / UGTIA9 |
Research Abstract |
Since glucuronidation is an important metabolic reaction for xenobiotic elimination, information on the induction or suppression of UDP-glucuronosyltransferase (UGT) enzymes at the isoform level is beneficial in drug therapy and the toxicological assessment of environmental chemicals. In this study, we focused on UGT1A isoforms (UGT1A1, UGT1A6 and UGT1A9), mainly expressed in the human liver, and examined the inducibility of UGT1As by β-naphthoflavone (BNF) in human hepatoma HepG2 cells. The cells were pretreated for 72 h with BNF at concentrations of 25, 50 and 100 μM. 7-Ethyl-10-hydroxycamptothecin (SN-38) glucuronidation, used as a probe for UGT1A1, showed sigmoidal kinetics with a Hill coefficient (n) of 1.2-1.3 in control and BNF-pretreated HepG2 cells. The V_<max> values were significantly increased 3.6- to 4.3-fold by BNF, whereas there was no significant change in the S_<50> values by BNF at any concentration examined. On the other hand, 4-methylumbelliferone (4-MU) glucuronida
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tion as a probe for UGT1A6 and UGT1A9 in the control and BNF-pretreated HepG2 cells exhibited a biphasic kinetic pattern Although K_<ml> values for the low-K_m phase were similar between the control and BNF-pretreated HepG2 cells, K_<m2> values for the high-K_m phase of BNF-pretreated liepG2 cells were reduced to 54-69% of control HepG2 cells. The values of V_<max> and V_<max2> for the low- and high-K_m phases, respectively, were significantly increased 1.9- to 2.6-fold by BNF at 25 and/or 50μM but not 100 μM With respect to V_<max> (V_<max1> and V_<max2>) and V_<max>/K_m (V_<max1>/K_<m1> and V_<max2>/K_<m2>), the values were significantly increased 2.0- to 3.2-fold by BNF at all concentrations examined. Furthermore, real-time reverse transcription polymerase chain reaction (RT-PCR) using TaqMan probes demonstrated that BNF concentration-dependently induced mRNA levels of UGTIA1 but not UGT1A6 or UGT1A9 in HepG2 cells (1.3- to 6.0-fold). These results suggest that the inducibility of UGT1A isoforms in HepG2 cells by BNF is different from other aryl hydrocarbon receptor (AhR) agonists previously reported, and should provide useful information for the prediction of drug-drug interactions and toxicological assessment of environmental chemicals. Less
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[Journal Article] Interaction of bisphenol A with human UDP-glucuronosyltransferase 1A6 enzyme2008
Author(s)
Hanioka, N., Takeda, Y., Tanaka-Kagawa, T., Hayashi, K., Jinno, H., and Narimatsu, S.
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Journal Title
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Influence of CYP2C19^*18 and CYP2C19^*19 alleles on omeprazole 5-hydroxylation: in vitro functional analysis of recombinant enzymes expressed in Saccharomyces cerevisiae2008
Author(s)
Hanioka, N., Tsuneto, Y., Saito, Y., Maekawa, K., Sawada, J., and Narimatsu, S.
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Journal Title
Basic Clin. Pharmacol. Toxicol. (印刷中)
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Functional characterization of two novel CYP2C19 variants (CYP2C19^*18 and CYP2C19^*19) found in a Japanese population2007
Author(s)
Hanioka, N., Tsuneto, Y., Saito, Y., Sumada, T., Maekawa, K., Saito, K., Sawada. J., and Narimatsu, S.
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Journal Title
Xenobiotica 37(4)
Pages: 342-355
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Functional characterization of human and cynomolgus monkey cytochrome P450 2E1 enzymes2007
Author(s)
Hanioka, N., Yamamoto, M., Iwabu, H., Jinno, H., Tanaka-Kagawa, T., Naito, S., Shimizu, T., Masuda, K., Katsu, T., and Narimatsu, S.
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Journal Title
Life Sci. 81(19-20)
Pages: 1436-1445
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Functional characterization of two novel CYP2C19 variants (CYP2C19*18 and CYP2C19*19) found in a Japanese population2007
Author(s)
Hanioka, N., Tsuneto, Y., Saito, Y., Sumada, T., Maekawa, K., Saito, K., Sawada, J., Narimatsu, S
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Journal Title
Xenobiotica 37 (4)
Pages: 342-355
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Functional characterization of human and cynomolgus monkey cytochrome P450 2E1 enzymes2007
Author(s)
Hanioka, N., Yamamoto, M., Iwabu, H., Jinno, H., Tanaka-Kagawa, T., Naito, S., Shimizu, T., Masuda, K., Katsu, T., Narimatsu, S
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Journal Title
Life Sci 81(19-20)
Pages: 1436-1445
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Catalytic roles of CYP2D6.10 and CYP2D6.36 enzymes in mexiletine metabolism: in vitro functional analysis of recombinant proteins expressed in Saccharomyces cerevisiae2006
Author(s)
Hanioka, N., Okumura, Y., Saito, Y., Hichiya, H., Soyama, A., Saito, K., Ueno, K., Sawada, J., and Narimatsu S.
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Journal Title
Biochem. Pharmacol. 71(9)
Pages: 1386-1395
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Inducibility of UDP-glucuronosyltransferase 1As by β-naphthoflavone in HepG2 cells2006
Author(s)
Hanioka, N., Obika, N., Nishimura, M., Jinno, H., Tanaka-Kagawa, T., Saito, K., Kiryu, K., Naito, S., and Narimatsu, S.
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Journal Title
Food Chem. Toxicol. 44(8)
Pages: 1251-1260
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Functional characterization of human and cynomolgus monkey UDP-glucuronosyltransferase 1A6 enzymes2006
Author(s)
Hanioka, N., Takeda, Y., Jinno, H., Tanaka-Kagawa, T, Naito, S., Koeda, A., Shimizu, T., Nomura, M., and Narimatsu, S.
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Journal Title
Chem. Biol. Interact. 164(1-2)
Pages: 136-145
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Catalytic roles of CYP2D6.10 and CYP2D6.36 enzymes in mexiletine metabolism : in vitro functional analysis of recombinant proteins expressed in Saccharoniyces cerevisiae2006
Author(s)
Hanioka, N., Okumura, Y., Saito, Y., Hichiya, H., Soyama, A., Saito, K., Ueno, K., Sawada, J., Narimatsu, S
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Journal Title
Biochem. Pharmacol 71 (9)
Pages: 1386-1395
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Inducibility of UDP-glucuronosyltransferase lAs by 13-naphthoflavone in HeoG2 cells2006
Author(s)
Hanioka, N., Obika, N., Nishimura, M., Jinno, H., Tanaka-Kagawa, T., Saito, K., Kiryu, K., Naito, S., Narimatsu, S
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Journal Title
Food Chem. Toxicol 44(8)
Pages: 1251-1260
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Functional characterization of human and cynomolgus monkey UDP-glucuronosyltransferase lA6 enzymes2006
Author(s)
Haitioka, N., Takeda, Y., Jinno, H., Tanaka-Kagawa, T., Naito, S., Koeda, A., Shimizu, T., Nomura, M., Narimatsu, S
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Journal Title
Chem. Biol. Interact 164(1-2)
Pages: 136-145
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Interaction of bisphenol A with human UDP-glucuronosyltransferase 1A6 enzyme
Author(s)
HanioIca, N., Takeda, Y., Tanaka-Kagawa, T., Hayashi, K., Jinno, H., Narimatsu, S
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Journal Title
Environ. Toxicol (in press)
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Influence of CYP2C19*18 and CYP2C19*19 alleles on omeprazole 5-hydroxylation : in vitro functional analysis of recombinant enzymes expressed in Saccharomyces cerevisiae
Author(s)
Hanioka, N., Tsuneto, Y., Saito, Y., Maekawa, K., Sawada, J., Narimatsu, S
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Journal Title
Basic Clin. Pharmacol. Toxicol (in press)
Description
「研究成果報告書概要(欧文)」より
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[Presentation] カニクイザルUGT2B20の酵素機能解析2007
Author(s)
長岡憲次郎, 風盛大地, 埴岡伸光, 清水剛文, 内藤真策, 成松鎭雄
Organizer
第46回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会
Place of Presentation
高知
Year and Date
2007-11-10
Description
「研究成果報告書概要(和文)」より
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[Presentation] Effect of SHP on transcriptional activities mediated by human HNF4α2007
Author(s)
Nakada, S., Saito, Y., Saeki, M., Sawada, J., Hanioka, N., Narimatsu, S
Organizer
46th Annual Meeting of Chugoku-Shikoku Branch of the Pharmaceutical Society of Japan
Place of Presentation
Kochi, Japan
Year and Date
2007-11-10
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Functional characterization of cynomolgus monkey UGT2B202007
Author(s)
Nagaoka, K., Kazamori, D., Hanioka, N., Shimizu, T., Naito, S., Narimatsu, S
Organizer
46th Annual Meeting of Chugoku-Shikoku Branch of the Pharmaceutical Society of Japan
Place of Presentation
Kochi, Japan
Year and Date
2007-11-10
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Hydrolysis of profluthrin, the highly-volatile pyrethroid insecticides, by human carboxylesterases2007
Author(s)
Tanaka-Kagawa, T., Hanioka, N., Matsumoto, T., Tokunaga, H., Narimatsu, S., Jinno, H
Organizer
Forum 2007 : Pharmaceutical Health Science and Environmental Toxicology
Place of Presentation
Osaka, Japan
Year and Date
2007-11-01
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Functional characterization of human and cynomolgus monkey cytochrome P450 2E1 enzymes2007
Author(s)
山本真紀, 岩部寛之, 米本麗, 増田和文, 勝孝, 埴岡伸光, 神野透人, 香川(田中)聡子, 内藤真策, 清水剛文, 成松鎭雄
Organizer
第8回国際薬物動態学会
Place of Presentation
仙台
Year and Date
2007-10-10
Description
「研究成果報告書概要(和文)」より
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[Presentation] Functional characterization of human and cynomolgus monkey cytochrome P450 2E1 enzymes2007
Author(s)
Yamanoto, M., Iwabu, H., Yonemoto, R., Masuda, K., Katsu, T., Hanioka, N., Jinno, H., Tanaka-Kagawa, T., Naito, S., Shimizu, T., Narimatsu, S
Organizer
8th International ISSX Meeting
Place of Presentation
Sendai, Japan
Year and Date
2007-10-10
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Characterization of cynomolgus monkey UGT1A6 : comparison with human UGT1A62007
Author(s)
Hanioka, N., Takeda, Y., Jinno, H., Tanaka-Kagawa, T., Naito, S., Shimizu, T., Narimatsu, S
Organizer
8th International ISSX Meeting
Place of Presentation
Sendai, Japan
Year and Date
2007-10-10
Description
「研究成果報告書概要(欧文)」より
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[Presentation] カニクイザル及びヒトCYP2E1の機能解析2007
Author(s)
山本真紀, 米本麗, 岩部寛之, 増田和文, 勝孝, 埴岡伸光, 香川(田中)聡子, 神野透人, 内藤真策, 清水剛文, 成松鎭雄
Organizer
日本薬学会第127年会
Place of Presentation
富山
Year and Date
2007-03-30
Description
「研究成果報告書概要(和文)」より
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[Presentation] Characterization of cynomolgus monkey UGT2B9 : comparison with human UGT2B72007
Author(s)
Shigeta, N., Shiga, S., Yamamoto, M., Hayashi, K., Takeda, Y., Hanioka, N., Naito, S., Shimizu, T., Narimatsu, S
Organizer
127th Annual Meeting of the Pharmaceutical Society of Japan
Place of Presentation
Toyama, Japan
Year and Date
2007-03-29
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Functional characterization of human and cynomolgus monkey cytochrome P450 2E1 enzymes2007
Author(s)
Yamanoto, M., Yonemoto, R, Iwabu, H., Masuda, K., Katsu, T., Hanioka, N., Tanaka-Kagawa, T., Jinno, H., Naito, S., Shimizu, T., Narimatsu, S
Organizer
127th Annual Meeting of the Pharmaceutical Society of Japan
Place of Presentation
Toyama, Japan
Year and Date
2007-03-29
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Functional characterization of two novel CYP2C19 variants (CYP2C19*18 and CYP2CI9*19) found in a Japanese population2006
Author(s)
Tsuneto, Y., Hanioka, N., Saito, Y., Sumada, T., Maekawa, K., Saito, K., Sawada, J., Narimatsu, S
Organizer
21st Annual Meeting of Japanese Society for the Study of Xenobiotics
Place of Presentation
Tokyo, Japan
Year and Date
2006-11-30
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Interaction of bisphenol A with human and cynomolgus monkey UDP-glucuronosyltransferase 1A6 enzyms2006
Author(s)
Takeda, Y., Tanaka-Kagawa, T., Jinno, H., Naito, S., Hanioka, N., Narimatsu, S
Organizer
Forum 2006 : Pharmaceutical Health Science and Environmental Toxicology
Place of Presentation
Tokyo, Japan
Year and Date
2006-10-30
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Characterization of cynomolgus monkey CYP2E1 : comparison with human CYP2E12006
Author(s)
Yamanoto, M., Yonemoto, R., Masuda, K., Katsu, T., Hanioka, N., Naito, S., Narimatsu, S
Organizer
Forum 2006 : Pharmaceutical Health Science and Environmental Toxicology
Place of Presentation
Tokyo, Japan
Year and Date
2006-10-30
Description
「研究成果報告書概要(欧文)」より
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[Presentation] 日本人で新たに見出された変異型CYP1A2の機能解析2006
Author(s)
經遠祐美, 礒部隆史, 埴岡伸光, 齋藤嘉朗, 前川京子, 香川(田中)聡子, 神野透人, 澤田純一, 成松鎭雄
Organizer
第45回日本薬学会・日本病院薬剤師会中国四国支部学術大会
Place of Presentation
広島
Year and Date
2006-10-28
Description
「研究成果報告書概要(和文)」より
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[Presentation] Construction of coexpression of CYP-fp2 using yeast expression vector pYES2006
Author(s)
Tsuji, S., Iwabu, H., M., Yamamoto, Takeda, Y., Torigoe, F., Hanioka, N., Narimatsu, S
Organizer
45th Annual Meeting of Chugoku-Shikoku Branch of the Pharmaceutical Society of Japan
Place of Presentation
Hiroshima, Japan
Year and Date
2006-10-28
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Functional analysis of three CYP1A2 variants found in a Japanese population2006
Author(s)
Tsuneto, Y., Isobe, T., Hanioka, N., Saito, Y., Maekawa, K., Tanaka-Kagawa, T., Jinno, H., Sawada, J., Narimatsu, S
Organizer
45th Annual Meeting of Chugoku-Shikoku Branch of the Pharmaceutical Society of Japan
Place of Presentation
Hiroshima, Japan
Year and Date
2006-10-28
Description
「研究成果報告書概要(欧文)」より
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