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2006 Fiscal Year Final Research Report Summary

Development of Environmental Risk Assessment System

Research Project

Project/Area Number 15201009
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Risk sciences of radiation/Chemicals
Research InstitutionHokkaido University

Principal Investigator

FUJITA Shoichi  Hokkaido University., Grad. School of Vet. Med., Professor, 大学院獣医学研究科, 教授 (10143314)

Co-Investigator(Kenkyū-buntansha) ISHIZUKA Mayumi  Hokkaido University., Grad. School of Vet. Med., Associate Professor., 大学院獣医学研究科, 助教授 (50332474)
SAKAMOTO Kentaro  Hokkaido University., Grad. School of Vet. Med., Instructor., 大学院獣医学研究科, 助手 (80374627)
Project Period (FY) 2003 – 2006
Keywordscytochrome P450 / microarray / wildlife / steroid hormone / environmental pollution / nuclear receptor / aryl hydrocarbon receptor
Research Abstract

The DNA microarray techniques are useful method to determine toxicological effects of xenobiotics, such as drugs and environmental chemicals, on the cells or experimental animals. To clarify the usefulness of DNA microarray method for wildlife samples, we collected wild Norway rats (rats) from urban areas, landfill and isolated island in Japan. Laboratory rats (Wistar) were used as control animals in this study. We measured the accumulation levels of polychlorinated dibenzo-p-dioxins (PCDD), furans (PCDF), polychlorinated biphenyls (PCBs), and organochlorine insecticides. We also examined the residue levels of polybrominated diphenyl ether (PBDE) in rat livers, which are used as flame retardants in plastics and rubbers. Additionally, we screened the alterations of mRNA in liver and testis of wild rats using DNA chip technique, and reported the relationships between accumulated contaminants and expression profiles of RNA. In this study, we also showed the genes which can be used as biomarkers.
To develop the DNA microarray for wild animals, we collected samples of wild and captive animals to compare the gene sequences. We cloned P450 and nuclear receptor genes from broad spectrum mammalians, birds and amphibians. We elucidated the possibility of microarray development for several wildlife species.
In current study, we also aimed at establishment of functional array which can assess the affinity of environmental chemicals to nuclear receptors. We determined the ligand affinities of nuclear receptors and cross-talk among xenobiotic receptors, e.g., arylhydrocarbon receptor, constitutive active receptor and peroxisome proliferator-activated receptors.

  • Research Products

    (46 results)

All 2007 2006 2005 2004 2003

All Journal Article (46 results)

  • [Journal Article] Plasma pharmacokinetics and CYP3A12-dependent metabolism of c-kit inhibitor imatinib in dogs.2007

    • Author(s)
      Ishizuka M. et al.
    • Journal Title

      Xenobiotica (In press)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Di-(2-ethylhexyl) phthalate suppresses tamoxifen-induced apoptosis in GH3 pituitary cells.2007

    • Author(s)
      Kim HS.et al.
    • Journal Title

      Arch Toxicol. (In press)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Elevated warfarin metabolism in warfarin-resitant roof rats (Rattus rattus) in Tokyo.2007

    • Author(s)
      Ishizuka M. et al.
    • Journal Title

      Drug Metab Dispos. 35

      Pages: 62-66

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Plasma pharmacokinetics and CYP3 A 12-dep endent metabolism of c-kit inhibitor imatinib in dogs.2007

    • Author(s)
      Ishizuka M, Nagai S, Sakamoto QK, Fujita S.
    • Journal Title

      Xenobiotica. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Di-(2-ethylhexyl) phthalate suppresses tamoxifen-induced apoptosis in GH3 pituitary cells.2007

    • Author(s)
      Kim HS, Ishizuka M, Kazusaka A, Fujita S.
    • Journal Title

      Arch Toxicol. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Elevated warfarin metabolism in warfarin-resitant roof rats (Rattus rattus) in Tokyo.2007

    • Author(s)
      Ishizuka M, Okajima F, Tanikawa T, Min H, Tanaka KD, Sakamoto KQ, Fujita S.
    • Journal Title

      Drug Metab Dispos. 35(1)

      Pages: 62-6

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Effect of lycopene and beta-carotene on peroxynitrite-mediated cellular modifications.2006

    • Author(s)
      Nuzandu K. et al.
    • Journal Title

      Toxicol Appl Pharmacol. 215

      Pages: 330-340

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] CYP2D-related metabolism in animals of the Canoidea superfamily -species differences.2006

    • Author(s)
      Ishizuka M. et al.
    • Journal Title

      Vet Res Commun. 30

      Pages: 505-512

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Induction of cytochrome P450-1A by the equine estrogen equilenin, a new endogenous aryl hydrocarbon receptor ligand.2006

    • Author(s)
      Jinnno A. et al.
    • Journal Title

      J Steroid Biochem Mol Biol. 98

      Pages: 48-55

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Maternal smoking during pregnancy and genetic polymorphisms in the Ah receptor, CYP1A1 and GSTM1 affect infant birth size in Japanese subjects.2006

    • Author(s)
      Sasaki et al.
    • Journal Title

      Mol Hum Reprod 12

      Pages: 77-83

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Effect of lycopene and beta-carotene on peroxynitrite-mediated cellular modifications.2006

    • Author(s)
      Muzandu K, Ishizuka M, Sakamoto KQ, Shaban Z, El Bohi K, Kazusaka A, Fujita S.
    • Journal Title

      Toxicol Appl Pharmacol. 215(3)

      Pages: 330-40

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] CYP2D-related metabolism in animals of the Canoidea superfamily-species differences.2006

    • Author(s)
      Ishizuka M, Lee JJ, Masuda M, Akahori F, Kazusaka A, Fujita S.
    • Journal Title

      Vet Res Commun. 30

      Pages: 505-12

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Induction of cytochrome P450-1A by the equine estrogen equilenin, a new endogenous aryl hydrocarbon receptor ligand.2006

    • Author(s)
      Jinno A, Maruyama Y, Ishizuka M, Kazusaka A, Nakamura A, Fujita S.
    • Journal Title

      J Steroid Biochem Mol Biol. 98(1)

      Pages: 48-55

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Maternal smoking during pregnancy and genetic polymorphisms in the Ah receptor, CYP1A1 and GSTM1 affect infant birth size in Japanese subjects.2006

    • Author(s)
      Sasaki S, Kondo T, Sata F, Saijo Y, Katoh S, Nakajima S, Ishizuka M, Fujita S, Kishi R.
    • Journal Title

      Mol Hum Reprod. 12(2)

      Pages: 77-83

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Possible involvement of peroxynitrite in estrogen-induced oxidative stress.2005

    • Author(s)
      Muzandu et al.
    • Journal Title

      Free Radical Research 39

      Pages: 389-398

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Importance of CYP2D3 in polymorphism of diazepam p-hydroxylation in rats.2005

    • Author(s)
      Sakai N. et al.
    • Journal Title

      Drug Metab Dispos 33

      Pages: 1675-1660

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] AhR and PPARα Antagonistic effects on CYP2B and CYP3A and additive inhibitory effects on CYP2C11.2005

    • Author(s)
      Shaban et al.
    • Journal Title

      Xenobiotica 52

      Pages: 163-172

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Effect of components of green tea extracts, caffeine and catechins on hepatic drug metabolizing enzyme activities and mutagenic transformation of carcinogens.2005

    • Author(s)
      Nikaidou et al.
    • Journal Title

      J Vet Med Sci 67

      Pages: 137-138

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Effect of components of green tea extracts, caffeine and catechins on hepatic drug metabolizing enzyme activities and mutagenic transformation of carcinogens.2005

    • Author(s)
      Nikaidou et al.
    • Journal Title

      Jpn J Vet Res. 52

      Pages: 173-184

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Lycopene and beta-carotene ameliorate catechol estrogen-mediated DNA damage.2005

    • Author(s)
      Muzandu et al.
    • Journal Title

      Jpn J Vet Res. 52

      Pages: 173-184

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Antigenotoxic effect of Pleurotus cornucopiae extracts on the mutagenesis of Salmonella typhimurium TA98 elicited by benzo[a]pyrene and oxidative DNA lesions in V79 hamster lung cells.2005

    • Author(s)
      El Bohi et al.
    • Journal Title

      Jpn J Vet Res. 52

      Pages: 163-172

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Possible involvement of peroxynitrite in estrogen-induced oxidative stress.2005

    • Author(s)
      Muzandu K, Shaban Z, Ishizuka M, Kazusaka A, Fujita S.
    • Journal Title

      Free Radical Research. 39(4)

      Pages: 389-398

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Importance of CYP2D3 in polymorphism of diazepam p-hydroxylation in rats.2005

    • Author(s)
      Sakai N, Saito K, Kim HS, Kazusaka A, Ishizuka M, Funae Y, Fujita S.
    • Journal Title

      Drug Metab Dispos. 2005 33(11)

      Pages: 1657-60

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] AhR and PPARa Antagonistic effects on CYP2B and CYP3A and additive inhibitory effects on CYP2C11.2005

    • Author(s)
      Shaban Z, Soliman M, El-shazly S, El-bohi K, Abdelazeez A, Kehelo K, Kim H, Muzandu K, Ishizuka M, Kazusaka A, Fujita S.
    • Journal Title

      Xenobiotica. 52(4)

      Pages: 163-172

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Effect of components of green tea extracts, caffeine and catechins on hepatic drug metabolizing enzyme activities and mutagenic transformation of carcinogens.2005

    • Author(s)
      Nikaidou S, Ishizuka M, Maeda Y, Hara T, Kazusaka A, Fujita S.
    • Journal Title

      J Vet Med Sci. 67(1)

      Pages: 137-138

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Effect of components of green tea extracts, caffeine and catechins on hepatic drug metabolizing enzyme activities and mutagenic transformation of carcinogens.2005

    • Author(s)
      Nikaidou S, Ishizuka M, Maeda Y, Hara Y, Kazusaka A, Fujita S.
    • Journal Title

      Jpn J Vet Res. 52(4)

      Pages: 185-92

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Lycopene and beta-carotene ameliorate catechol estrogen-mediated DNA damage.2005

    • Author(s)
      Muzandu K, El Bohi K, Shaban Z, Ishizuka M, Kazusaka A, Fujita S.
    • Journal Title

      Jpn J Vet Res. 52(4)

      Pages: 173-84

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Antigenotoxic effect of Pleurotus cornucopiae extracts on the mutagenesis of Salmonella typhimurium TA98 elicited by benzo[a]pyrene and oxidative DNA lesions in V79 hamster lung cells.2005

    • Author(s)
      El Bohi KM, Sabik L, Muzandu K, Shaban Z, Soliman M, Ishizuka M, Kazusaka A, Fujita S.
    • Journal Title

      Jpn J Vet Res. 52(4)

      Pages: 163-72

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Down regulation of hepatic PPARalpha function by AhR ligand.2004

    • Author(s)
      Shaban et al.
    • Journal Title

      J Vet Med Sci. 66

      Pages: 1377-1386

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Iodine intake as a possible cause of discontinuous decline in sperm counts : a re-evaluation of historical and geographic variation in semen quality.2004

    • Author(s)
      Sakamoto et al.
    • Journal Title

      Jpn J Vet Res 52

      Pages: 85-94

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Alterations of activities of cytosolic phospholipase A2 and arachid onic acid-metabolizing enzymes in di-(2-ethylhexyl)phthalate-induced testicular atrophy.2004

    • Author(s)
      Kim et al.
    • Journal Title

      Jpn J Vet Res 52

      Pages: 1119-1124

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Strain differences in diazepam metabolism at its three metabolic sites in sprague-dawley, brown norway, dark agouti, and wistar strain rats.2004

    • Author(s)
      Saito et al.
    • Journal Title

      Drug Metab Dispos 32

      Pages: 959-965

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Related PPARalpha-dependent modulation of hepatic CYP1A by clofibric acid in rats.2004

    • Author(s)
      Shaban et al.
    • Journal Title

      Arch Toxicol 78

      Pages: 496-507

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Polymorphism in diazepam metabolism in Wistar rats.2004

    • Author(s)
      Saito et al.
    • Journal Title

      J Pharm Sci. 93

      Pages: 1271-1278

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Down regulation of hepatic PPARalpha function by AhR ligand.2004

    • Author(s)
      Shaban, Z., El-Shazly, S., Abdelhady, S., Fattouh, I., Muzandu, K., Ishizuka M., Kimura, K., Kazusaka, A., Fujita, S.
    • Journal Title

      J Vet Med Sci. 66(11)

      Pages: 1377-86

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Iodine intake as a possible cause of discontinuous decline in sperm counts : a re-evaluation of historical and geographic variation in semen quality.2004

    • Author(s)
      Sakamoto KQ., Ishizuka M., Kazusaka, A., Fujita, S.
    • Journal Title

      Jpn J Vet Res. 52(2)

      Pages: 85-94

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Alterations of activities of cytosolic phospholipase A2 and arachidonic acid-metabolizing enzymes in di-(2-ethylhexyl)phthalate-induced testicular atrophy.2004

    • Author(s)
      Kim HS, Ishizuka M, Kazusaka A, Fujita S.
    • Journal Title

      J Vet Med Sci. 66(9)

      Pages: 1119-24

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Strain differences in diazepam metabolism at its three metabolic sites in sprague-dawley, brown norway, dark agouti, and wistar strain rats.2004

    • Author(s)
      Saito K, Sakai N, Kim HS, Ishizuka M, Kazusaka A, Fujita, S.
    • Journal Title

      Drug Metab Dispos. 32(9)

      Pages: 959-65

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Related PPARalpha-dependent modulation of hepatic CYP1A by clofibric acid in rats.2004

    • Author(s)
      Shaban Z, El-Shazly S, Ishizuka M, Kimura K, Kazusaka A, Fujita, S.
    • Journal Title

      Arch Toxicol. 78(9)

      Pages: 496-507

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Polymorphism in diazepam metabolism in Wistar rats.2004

    • Author(s)
      Saito K, Kim HS, Sakai N, Ishizuka M, Kazusaka A, Fujita, S.
    • Journal Title

      J Pharm Sci. 93(5)

      Pages: 1271-8

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Short period exposure to di-(2-ethylhexyl) phthalate regulates testosterone metabolism in testis of prepubertal rats.2003

    • Author(s)
      Kim HS.et al.
    • Journal Title

      Arch Toxicol. 77

      Pages: 446-451

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Perinatal exposure to low doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin alters sex-dependent expression of hepatic CYP2C11.2003

    • Author(s)
      Ishizuka et al.
    • Journal Title

      J Biochem Mol Toxicol 17

      Pages: 278-285

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Cytochrome p450 induction and gonadal status alteration in common carp (Cyprinus carpio) associated with the discharge of dioxin contaminated effluent to the Hikiji River, Kanagawa Prefecture, Japan.2003

    • Author(s)
      Sakamoto et al.
    • Journal Title

      Chemosphere 51

      Pages: 491-500

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Short period exposure to di-(2-ethylhexyl) phthalate regulates testosterone metabolism in testis of prepubertal rats.2003

    • Author(s)
      Kim, HS, Saito K, Ishizuka M, Kazusaka A, Fujita S.
    • Journal Title

      Arch Toxicol. 77(8)

      Pages: 446-51

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Perinatal exposure to low doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin alters sex-dependent expression of hepatic CYP2C11.2003

    • Author(s)
      Ishizuka M, Yonemoto J, Zaha H, Tohyama C, Sone H.
    • Journal Title

      J Biochem Mol Toxicol. 17(5)

      Pages: 278-85

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Cytochrome p450 induction and gonadal status alteration in common carp (Cyprinus carpio) associated with the discharge of dioxin contaminated effluent to the Hikiji River, Kanagawa Prefecture, Japan.2003

    • Author(s)
      Sakamoto KQ, Nakai K, Aoto T, Yokoyama A, Ushikoshi R, Hirose H, Ishizuka M, Kazusaka A, Fujita S.
    • Journal Title

      Chemosphere. 51(6)

      Pages: 491-500

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2008-05-27  

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