2005 Fiscal Year Final Research Report Summary
Mechanism of benzene-induced hematopoietic disturbances mediated by arylhydrocarbon receptors
| Project/Area Number |
15510064
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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 |
Risk sciences of radiation/Chemicals
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| Research Institution | National Institute of Health Sciences |
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Principal Investigator |
INOUE Tohru National Institute of Health Sciences, Center for Biological Safety and Research, Director, 安全性生物試験研究センター, センター長 (50100110)
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| Co-Investigator(Kenkyū-buntansha) |
HIRABAYASHI Yoko National Institute for Health Sciences, Center for Biological Safety and Research, Cellular and Molecular Toxicology Division, Section Chief, 安全性生物試験研究センター毒性部, 室長 (30291115)
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| Project Period (FY) |
2003 – 2005
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| Keywords | Arylhydrocarbon receptor (AhR) / hemopoietic stem cell / cell cycle / BUUV method / AhR knockout mouse / suppression of the hemopoiesis / benzene / benzene metabolites |
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| Research Abstract |
Research subject of this report was originally based on a fundamental discovery that the benzene-induced hematopoietic toxicity was nullified in the aryl hydrocarbon receptor (AhR) knockout (KO) mice. Utilizing this as a model, thus, the aim of the research subject was to proceed research on an experimental model for elucidation of mechanism underlying receptor-mediated chemical toxicity.
Outcome of the original publications includes an elucidation of unique biological function of AhRs. A cell cycle related study of the hemopoietic stem/progenitor concerns, by the AhR, primitive progenitor cells are maintained in the slower cell cycling with possible dormant fraction, whereas mature progenitor cells are in the faster cell cycling. In AhR knockout mice, benzene exposure has been known not to express p21^<waf1>, cell cycle dependent kinase inhibitor. In this regard, it is of interest that mice carrying human thioredoxin gene over-expressed shows a down modulation of AhR during benzene exposure, which may have a possible relevancy to the attenuation of the benzene-induced hematotoxicity in Trx-Tg mice. Another study related to AhR expression after benzene exposure is to define the possible site of benzene-induced hematotoxicity by means of bone marrow transplantation which shows that the hematotoxicity after benzene exposure is solely from the repopulated AhR deficient bone marrow cells. There seems to be another possibility of benzene-induced peripheral blood toxicity, which is presumably based on the hepatic xenobiotic response other than repopulated bone marrow.
Progresses mentioned above are essentially published elsewhere.
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[Journal Article] Meeting report: Validation of toxicogenomics-based test systems: ECVAM-ICCVAM/NICEATM considerations for regulatory use.2006
Author(s)
Corvi R, Ahr HJ, Albertini S, Blakey DH, Clerici L, Coecke S, Douglas GP, Gribaldo L, Groten JP, Haase B, Hamernik K, Hartung T, Inoue T, Indans I, Maurici D, Orphanides G, Rembges D, Sansone SA, Snape JP, Toda E, Tong W, van Delft JH, Weis B, Schechtman LM
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Journal Title
Environ Health Perspect 114(3)
Pages: 420-429
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] MX, a by-product of water chlorination, lacks in vivo genotoxicity in gpt delta mice but inhibits gap junctional intercellular communication in rat WB cells.2005
Author(s)
Nishikawa A, Sai K, Okazaki K, Son HY, Kanki K, Nakajima M, Kinae N, Nohmi T, Trosko JE, Inoue T, Hirose M
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Eloctron microscopical evidence of the protective function of thioredoxin (Trx/ADF) transgene against 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced cellular toxicity in the liver and brain.2005
Author(s)
Yoon BI, Kaneko T, Hirabayashi Y, Imazawa T, Nishikawa A, Kodama Y, Kanno J, Yodoi J, Han JH, Hirose M, Inoue T
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Journal Title
J Toxicol Pathol 18
Pages: 41-46
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] The utility of genetically modified mouse assays for identifying human carcinogens: a basic understanding and path forward. The Alternatives to Carcinogenicity Testing Committee ILSI HESI.2004
Author(s)
MacDonald J, French JE, Gerson RJ, Goodman J, Inoue T, Jacobs A, Kasper P, Keller D, Lavin A, Long G, McCullough B, Sistare FD, Storer R, van der Laan JW
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Journal Title
Toxicol Sci 77(2)
Pages: 188-194
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Mechanisms of benzene-induced hematotoxicity and leukemogenicity: cDNA microarray analyses using mouse bone marrow tissue.2003
Author(s)
Yoon BI, Li GX, Kitada K, Kawasaki Y, Igarashi K, Kodama Y, Inoue T, Kobayashi K, Kanno J, Kim DY, Inoue T, Hirabayashi Y
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Journal Title
Environ Health Perspect 111(11)
Pages: 1411-1420
Description
「研究成果報告書概要(欧文)」より
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[Book] On the Mechanistic Differences of Benzene-induced Leukemogenesis between Wild type and p53 Knockout Mice. Molecular Mechanisms for Radiation-induced Cellular Response and Cancer Development. (Eds: Tanaka K, Takabatake T, Fujikawa K, Matsumoto T, Sato F.)2003
Author(s)
Hirabayashi Y, Yoon BI, Kawasaki Y, Li GX, Kanno J, Inoue T
Total Pages
110-116
Publisher
Aomori, Institute for Environmental Sciences:
Description
「研究成果報告書概要(欧文)」より
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[Book] Connexin 32 (Cx32) Plays Double Functions, a Promotion and a Protection, for the Chemically Induced Leukemogenesis. Molecular Mechanisms for Radiation-induced Cellular Response and Cancer Development. (Eds: Tanaka K, Takabatake T, Fujikawa K, Matsumoto T, Sato F. )2003
Author(s)
Hirabayashi Y, Yoon BI, Tsuboi I, Huo Y, Kodama Y, Otto T, Kanno J, Willeck K, Trosko JE, Inoue T
Total Pages
143-149
Publisher
Aomori, Institute for Environmental Sciences
Description
「研究成果報告書概要(欧文)」より
