Sayaka Mizukami

Tokyo University of Agriculture, Edo, Tōkyō, Japan

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Publications (15)51.87 Total impact

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    ABSTRACT: To elucidate the maternal exposure effects of aflatoxin B1 (AFB1) and its metabolite aflatoxin M1, which is transferred into milk, on postnatal hippocampal neurogenesis, pregnant Sprague-Dawley rats were provided a diet containing AFB1 at 0, 0.1, 0.3, or 1.0ppm from gestational day 6 to day 21 after delivery on weaning. Offspring were maintained through postnatal day (PND) 77 without AFB1 exposure. Following exposure to 1.0ppm AFB1, offspring showed no apparent systemic toxicity at weaning, whereas dams showed increased liver weight and DNA repair gene upregulation in the liver. In the hippocampal dentate gyrus of male PND 21 offspring, the number of doublecortin(+) progenitor cells were decreased, which was associated with decreased proliferative cell population in the subgranular zone at ≥ 0.3ppm, although T-box brain 2(+) cells, tubulin beta III(+) cells, gamma-H2A histone family, member X(+) cells, and cyclin-dependent kinase inhibitor 1A(+) cells did not fluctuate in number. AFB1 exposure examined at 1.0ppm also resulted in transcript downregulation of the cholinergic receptor subunit Chrna7 and dopaminergic receptor Drd2 in the dentate gyrus, although there was no change in transcript levels of DNA repair genes. In the hippocampal dentate hilus, interneurons expressing CHRNA7 or phosphorylated tropomyosin receptor kinase B (TRKB) decreased at ≥ 0.3ppm. On PND 77, there were no changes in neurogenesis-related parameters. These results suggested that maternal AFB1 exposure reversibly affects hippocampal neurogenesis targeting type-3 progenitor cells. This mechanism likely involves suppression of cholinergic signals on hilar GABAergic interneurons and brain-derived neurotrophic factor-TRKB signaling from granule cells. The no-observed-adverse-effect level for offspring neurogenesis was determined to be 0.1ppm (7.1-13.6mg/kg body weight/day). Copyright © 2015. Published by Elsevier Ireland Ltd.
    Toxicology 08/2015; DOI:10.1016/j.tox.2015.08.001 · 3.75 Impact Factor
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    ABSTRACT: Developmental exposure to cuprizone (CPZ), a demyelinating agent, impairs intermediate-stage neurogenesis in the hippocampal dentate gyrus of rat offspring. To investigate the possibility of alterations in adult neurogenesis following postpubertal exposure to CPZ in a framework of general toxicity studies, CPZ was orally administered to 5-week-old male rats at 0, 120, or 600mg/kg body weight/day for 28days. In the subgranular zone (SGZ), 600mg/kg CPZ increased the number of cleaved caspase-3(+) apoptotic cells. At ≥120mg/kg, the number of SGZ cells immunoreactive for TBR2, doublecortin, or PCNA was decreased, while that for SOX2 was increased. In the granule cell layer, CPZ at ≥120mg/kg decreased the number of postmitotic granule cells immunoreactive for NEUN, CHRNA7, ARC or FOS. In the dentate hilus, CPZ at ≥120mg/kg decreased phosphorylated TRKB(+) interneurons, although the number of reelin(+) interneurons was unchanged. At 600mg/kg, mRNA levels of Bdnf and Chrna7 were decreased, while those of Casp4, Casp12 and Trib3 were increased in the dentate gyrus. These data suggest that CPZ in a scheme of 28-day toxicity study causes endoplasmic reticulum stress-mediated apoptosis of granule cell lineages, resulting in aberrations of intermediate and late-stage neurogenesis and following suppression of immediate early gene-mediated neuronal plasticity. Suppression of BDNF signals to interneurons caused by decreased cholinergic signaling may play a role in these effects of CPZ. The effects of postpubertal CPZ on neurogenesis were similar to those observed with developmental exposure, except for the lack of reelin response, which may contribute to the greater decrease in SGZ cells. Copyright © 2015. Published by Elsevier Inc.
    Toxicology and Applied Pharmacology 06/2015; DOI:10.1016/j.taap.2015.06.005 · 3.63 Impact Factor
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    ABSTRACT: Hexachlorophene (HCP) has been shown to induce myelin vacuolation due to intramyelinic edema of the nerve fibers in animal neural tissue. We investigated the maternal exposure effect of HCP on hippocampal neurogenesis in the offspring of pregnant mice supplemented with 0 (control), 33 or 100 ppm HCP in diet from gestational day 6 to day 21 after delivery. On postnatal day (PND) 21, offspring as examined in males exhibited decreased granule cell lineage populations expressing paired box 6, sex-determining region Y-box 2 and eomesodermin in the hippocampal subgranular zone (SGZ) accompanied by myelin vacuolation involving white matter tracts of the hippocampal fimbria at ≥ 33 ppm. However, SGZ cellular populations expressing brain lipid binding protein and doublecortin were unchanged at any dose. Transcript expression of cholinergic receptor genes, Chrna4 and Chrnb2, and glutamate receptor genes, Grm1 and Grin2d, examined at 100 ppm, decreased in the dentate gyrus. HCP exposure did not alter the number of proliferating or apoptotic cells in the SGZ, or reelin- or calcium-binding protein-expressing γ-aminobutyric acid (GABA)ergic interneurons in the dentate hilus, on PND 21 and PND 77. All neurogenesis-related changes observed in HCP-exposed offspring on PND 21 disappeared on PND 77, suggesting that maternal HCP exposure at ≥ 33 ppm reversibly decreased type 2 intermediate-stage progenitor cells in the hippocampal neurogenesis. Myelin vacuolation might be responsible for changes in neurogenesis possibly by reducing nerve conduction velocity of cholinergic inputs from the septal-hippocampal pathway to granule cell lineages and/or GABAergic interneurons, and of glutamatergic inputs to granule cell lineages. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.
    Journal of Applied Toxicology 05/2015; DOI:10.1002/jat.3162 · 3.17 Impact Factor
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    ABSTRACT: We have previously reported that a 28-day treatment of carcinogens evoking target cell proliferation activates G1 /S checkpoint function and apoptosis, as well as induction of aberrant ubiquitin D (Ubd) expression, suggesting disruptive spindle checkpoint function, in rats. The present study aimed to determine the onset time of rat liver cells to undergo carcinogen-specific cell cycle aberration and proliferation. Animals were treated orally with a hepatocarcinogenic dose of methyleugenol or thioacetamide for 3, 7 or 28 days. For comparison, some animals were subjected to partial hepatectomy or treated with noncarcinogenic hepatotoxicants (acetaminophen, α-naphthyl isothiocyanate or promethazine). Carcinogen-specific liver cell kinetics appeared at day 28 as evident by increases of cell proliferation, p21(Cip1+) cells, phosphorylated-Mdm2(+) cells and cleaved caspase 3(+) cells, and upregulation of DNA damage-related genes. Hepatocarcinogens also downregulated Rbl2 and upregulated Cdkn1a and Mdm2, and decreased Ubd(+) cells co-expressing phosphorylated-histone H3 (p-Histone H3) and p-Histone H3(+) cell ratio within the Ki-67(+) proliferating population. These results suggest that it takes 28 days to induce hepatocarcinogen-specific early withdrawal of proliferating cells from M phase due to disruptive spindle checkpoint function as evidenced by reduction of Ubd(+) cells staying at M phase. Disruption of G1 /S checkpoint function reflected by downregulation of Rbl2 as well as upregulation of Mdm2 suggestive of sequestration of retinoblastoma protein is responsible for the facilitation of carcinogen-induced cell proliferation at day 28. Accumulation of DNA damage probably in association with facilitation of p53 degradation by activation of Mdm2 may be a prerequisite for aberrant p21(Cip1) activation, which is responsible for apoptosis. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.
    Journal of Applied Toxicology 05/2015; DOI:10.1002/jat.3163 · 3.17 Impact Factor
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    ABSTRACT: Azoxymethane (AOM) is a potent carcinogen used for induction of colon tumors in rats and mice. It is also known that AOM treatment induces small bowel tumors in addition to colorectal tumors in rats. The present study examined the histogenesis of AOM-induced rat duodenal tumors in comparison with concurrently induced colorectal tumors by histochemical and immunohistochemical approaches. Duodenal and colorectal tumors were positive for both periodic acid-Schiff reaction and Alcian blue staining. Immunohistochemically, duodenal tumors were positive for intestinal epithelial markers such as cytokeratin (CK) 20 (100%) and mucin (MUC) 2 (91.7%) but negative for pancreaticobiliary markers such as CK7 (100%) and MUC1 (100%). All colorectal tumors were also negative for CK7 and MUC1 but positive for CK20. Eighty percent of colorectal tumors were positive for MUC2. In addition, nuclear accumulation of β-catenin was found in duodenal tumors (70.8%), which was similar to colorectal tumors (90.0%). These results indicate that duodenal tumors induced by AOM treatment of rats were derived from intestinal epithelium. Similar to colorectal tumors, nuclear accumulation of β-catenin indicates activation of Wnt signaling as a driving force for tumor progression in AOM-induced duodenal tumors. Copyright © 2015 Elsevier GmbH. All rights reserved.
    Experimental and toxicologic pathology: official journal of the Gesellschaft fur Toxikologische Pathologie 04/2015; 67(5-6). DOI:10.1016/j.etp.2015.03.002 · 2.01 Impact Factor
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    ABSTRACT: The exposure to cuprizone (CPZ) leads to demyelination in the central nervous system in rodents. To examine the developmental effects of CPZ exposure on hippocampal neurogenesis, pregnant rats were treated with 0, 0.1 or 0.4% CPZ in the diet from gestational day 6 to day 21 after delivery. On postnatal day 21, male offspring had a decreased density of new glue2(+) oligodendrocyte progenitor cells in the dentate hilus and in the area of the cerebellar medulla in the presence of 0.4% CPZ. With regard to neurogenesis parameters, offspring had decreased T box brain 2(+) progenitor cells and increased apoptotic cells, as detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling, which was accompanied by the up-regulation of Casp12 and Bcl2l11 in the subgranular zone, and increased reelin(+) interneurons in the dentate hilus. In addition, the density of phosphorylated TrkB(+) interneurons decreased in the dentate hilus, which was accompanied by transcript down-regulation of Bdnf and Chrna7 in the dentate gyrus. Moreover, granule cells expressing gene products of immediate-early genes, i.e., Arc and Fos, decreased. These results suggest that maternal exposure to 0.4% CPZ decreases proliferative type-2 progenitor cells via endoplasmic reticulum stress-mediated apoptosis and inhibition of cholinergic signals to intermediate-stage progenitor cells following reduced oligodendrocyte production and suppression of the brain-derived neurotrophic factor signaling cascade. Increases in reelin-expressing interneurons may compensate for impaired granule cell migration and/or correct positioning due to decreased immediate-early gene-mediated neuronal plasticity. However, all observed fluctuations disappeared at the adult stage, suggesting that CPZ-induced developmental neurotoxicity was reversible. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Toxicology Letters 02/2015; 234(3). DOI:10.1016/j.toxlet.2015.01.022 · 3.36 Impact Factor
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    ABSTRACT: Both developmental and adult-stage hypothyroidism disrupt rat hippocampal neurogenesis. We previously showed that exposing mouse offspring to manganese permanently disrupts hippocampal neurogenesis and abolishes the asymmetric distribution of cells expressing Mid1, a molecule regulated by sonic hedgehog (Shh) signaling. The present study examined the involvement of Shh signaling on the disruption of hippocampal neurogenesis in rats with hypothyroidism. Pregnant rats were treated with methimazole (MMI) at 0 or 200 ppm in the drinking water from gestation day 10 to 21 days after delivery (developmental hypothyroidism). Adult male rats were treated with MMI in the same manner from postnatal day (PND) 46 to PND 77 (adult-stage hypothyroidism). Developmental hypothyroidism reduced the number of Mid1(+) cells within the subgranular zone of the dentate gyrus of offspring on PND 21, and consequently abolished the normal asymmetric predominance of Mid1(+) cells on the right side through the adult stage. In control animals, Shh was expressed in a subpopulation of hilar neurons, showing asymmetric distribution with left side predominance on PND 21; however, this asymmetry did not continue through the adult stage. Developmental hypothyroidism increased Shh(+) neurons bilaterally and abolished the asymmetric distribution pattern on PND 21. Adult hypothyroidism also disrupted the asymmetric distribution of Mid1(+) cells but did not affect the distribution of Shh(+) hilar neurons. The results suggest that the hippocampal neurogenesis disruption seen in hypothyroidism involves changes in asymmetric Shh(+) neuron distribution in developmental hypothyroidism and altered Mid1 expression in both developmental and adult-stage hypothyroidism. © The Author 2014. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email:
    Toxicological Sciences 12/2014; 144(1). DOI:10.1093/toxsci/kfu266 · 4.48 Impact Factor
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    ABSTRACT: Hexachlorophene (HCP) is known to induce myelin vacuolation corresponding to intramyelinic edema of nerve fibers in the central and peripheral nervous system in animals. This study investigated the effect of maternal exposure to HCP on hippocampal neurogenesis in rat offspring using pregnant rats supplemented with 0 (controls), 100, or 300ppm HCP in the diet from gestational day 6 to day 21 after delivery. On postnatal day (PND) 21, the numbers of T box brain 2 (+) progenitor cells and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (+) apoptotic cells in the hippocampal subgranular zone (SGZ) decreased in female offspring at 300ppm, which was accompanied by myelin vacuolation and punctate tubulin beta-3 chain staining of nerve fibers in the hippocampal fimbria. In addition, transcript levels of the cholinergic receptor, nicotinic beta 2 (Chrnb2) and B-cell CLL/lymphoma 2 (Bcl2) decreased in the dentate gyrus. HCP-exposure did not alter the numbers of SGZ proliferating cells and reelin- or calcium-binding protein-expressing γ-aminobutyric acid (GABA)-ergic interneuron subpopulations in the dentate hilus on PND 21 and PND 77. Although some myelin vacuolation remained, all other changes observed in HCP-exposed offspring on PND 21 disappeared on PND 77. These results suggest that maternal HCP exposure reversibly decreases type-2b intermediate-stage progenitor cells via the mitochondrial apoptotic pathway in offspring hippocampal neurogenesis at 300ppm HCP. Neurogenesis may be affected by dysfunction of cholinergic inputs into granule cell lineages and/or GABAergic interneurons as indicated by decreased transcript levels of Chrnb2 and numbers of Chrnb2(+) interneurons caused by myelin vacuolation in the septal-hippocampal pathway. Copyright © 2014. Published by Elsevier Ireland Ltd.
    Toxicology 12/2014; 328. DOI:10.1016/j.tox.2014.12.009 · 3.75 Impact Factor
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    ABSTRACT: 3,3’-Iminodipropionitrile (IDPN) causes neurofilament (NF)-filled swellings in the proximal segments of many large-caliber myelinated axons. This study investigated the effect of maternal exposure to IDPN on hippocampal neurogenesis in rat offspring using pregnant rats supplemented with 0 (controls), 67 or 200 ppm IDPN in drinking water from gestational day 6 to day 21 after delivery. On postnatal day (PND) 21, female offspring subjected to analysis had decreased parvalbumin+, reelin+ and phospho-TrkB+ interneurons in the dentate hilus at 200 ppm and increased granule cell populations expressing immediate-early gene products, Arc or c-Fos, at ≥ 67 ppm. mRNA expression in the dentate gyrus examined at 200 ppm decreased with brain-derived neurotrophic factor (Bdnf) and very low density lipoprotein receptor. Immunoreactivity for phosphorylated NF heavy polypeptide decreased in the molecular layer of the dentate gyrus and the stratum radiatum of the cornu ammonis (CA) 3, portions showing axonal projections from mossy cells and pyramidal neurons, at 200 ppm on PND 21, whereas immunoreactivity for synaptophysin was unchanged in the dentate gyrus. Observed changes all disappeared on PND 77. There were no fluctuations in the numbers of apoptotic cells, proliferating cells and subpopulations of granule cell lineage in the subgranular zone on PND 21 and PND 77. Thus, maternal IDPN exposure may reversibly affect late-stage differentiation of granule cell lineages involving neuronal plasticity as evident by immediate-early gene responses to cause BDNF downregulation resulting in a reduction in parvalbumin+ or reelin+ interneurons and suppression of axonal plasticity in the mossy cells and CA3 pyramidal neurons. Copyright © 2014 John Wiley & Sons, Ltd.
    Journal of Applied Toxicology 11/2014; 35(8). DOI:10.1002/jat.3086 · 3.17 Impact Factor
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    ABSTRACT: To clarify the involvement of signaling of transforming growth factor (TGF)-β during the hepatocarcinogenesis, the immunohistochemical distribution of related molecules was analyzed in relation with liver cell lesions expressing glutathione S-transferase placental form (GST-P) during liver tumor promotion by fenbendazole, phenobarbital, piperonyl butoxide, or thioacetamide, using rats. Our study focused on early-stage promotion (6 weeks after starting promotion) and late-stage promotion (57 weeks after starting promotion). With regard to Smad-dependent signaling, cytoplasmic accumulation of phosphorylated Smad (phospho-Smad)-2/3 — identified as Smad3 by later immunoblot analysis — increased in the subpopulation of GST-P+ foci, while Smad4, a nuclear transporter of Smad2/3, decreased during early-stage promotion. By late-stage promotion, GST-P+ lesions lacking phospho-Smad2/3 had increased in accordance with lesion development from foci to carcinomas, while Smad4 largely disappeared in most proliferative lesions. With regard to Smad-independent mitogen-activated protein kinases, GST-P+ foci that co-expressed phospho-p38 mitogen-activated protein kinase increased during early-stage promotion; however, p38-downstream phospho-activating transcriptional factor (ATF)-2, ATF3, and phospho-c-Myc, were inversely downregulated without relation to promotion. By late-stage promotion, proliferative lesions downregulated phospho-ATF2 and phospho-c-Myc along with lesion development, as with downregulation of phospho-p38 in all lesions. These results suggest that from the early stages, carcinogenic processes were facilitated by disruption of tumor suppressor functions of Smad-dependent signaling, while Smad-independent activation of p38 was an early-stage phenomenon. GST-P− foci induced by promotion with agonists of peroxisome proliferator-activated receptor-α did not change Smad expression, suggesting an aberration in the Smad-dependent signaling prerequisites for induction of GST-P+ proliferative lesions.
    Toxicology and Applied Pharmacology 08/2010; 246(3-246):128-140. DOI:10.1016/j.taap.2010.04.016 · 3.63 Impact Factor
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    ABSTRACT: Wy-14,643 (WY), a peroxisome proliferator-activated receptor-alpha agonist, and piperonyl butoxide (PBO), a pesticide synergist, induce oxidative stress and promote hepatocarcinogenesis in the liver of rodents. These chemicals belong to a class of non-genotoxic carcinogens, but DNA damage secondary to the oxidative stress resulting from reactive oxygen species generation is suspected in rodents given these chemicals. To examine whether WY or PBO have DNA-damaging potential in livers of rats subjected to repeated oral administration for 14 days, the in vivo liver comet assay was performed in partially hepatectomized rats, and the expression of some DNA-repair genes was examined. Then, to examine whether they have genotoxic potential, the in vivo liver initiation assay was performed in rats. In the comet assay, positive results were obtained at 3 h after the last treatment of WY, and some DNA-repair genes such as Apex1, Mlh1, Xrcc5, and Gadd45 were up-regulated in the liver. In the liver initiation assay, negative results were obtained for both WY and PBO. The results of the present study suggest that WY, but not PBO, causes some DNA damage in livers of rats, but such DNA damage was repaired by the increased activity of some DNA repair genes and may not lead to a DNA mutation.
    Archives of Toxicology 06/2010; 84(6):493-500. DOI:10.1007/s00204-010-0516-x · 5.08 Impact Factor
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    ABSTRACT: To elucidate the role of metal-related molecules in hepatocarcinogenesis, we examined immunolocalization of transferrin receptor (Tfrc), ceruloplasmin (Cp) and metallothionein (MT)-1/2 in relation to liver cell foci positive for glutathione-S-transferase placental form (GST-P) in the early stage of tumor promotion by fenbendazole (FB), phenobarbital, piperonyl butoxide or thioacetamide in a rat two-stage hepatocarcinogenesis model. To estimate the involvement of oxidative stress responses to the promotion, immunolocalization of 4-hydroxy-2-nonenal, malondialdehyde and acrolein was similarly examined. Our findings showed that MT-1/2 immunoreactivity was not associated with the cellular distribution of GST-P and proliferating cell nuclear antigen, suggesting no role of MT-1/2 in hepatocarcinogenesis. We also found enhanced expression of Tfrc after treatment with strong tumor-promoting chemicals. With regard to Cp, the population showing down-regulation was increased in the GST-P-positive foci in relation to tumor promotion. Up-regulation of Tfrc and down-regulation of Cp was maintained in GST-P-positive neoplastic lesions induced after long-term promotion with FB, suggesting the expression changes occurring downstream of the signaling pathway involved in the formation of GST-P-positive lesions. Furthermore, enhanced accumulation of lipid peroxidation end products was observed in the GST-P-positive foci by promotion. Post-initiation treatment with peroxisome proliferator-activated receptor alpha agonists did not enhance any such distribution changes in GST-P-negative foci. The results thus suggest that facilitation of lipid peroxidation is involved in the induction of GST-P-positive lesions by tumor promotion from an early stage, and up-regulation of Tfrc and down-regulation of Cp may be a signature of enhanced oxidative cellular stress in these lesions.
    Archives of Toxicology 04/2010; 84(4):319-31. DOI:10.1007/s00204-009-0496-x · 5.08 Impact Factor
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    ABSTRACT: To investigate liver tumor promotion mechanisms of copper (Cu)- and iron (Fe)-overloading, immunolocalization of metal-related biomolecules and lipid peroxidation end products was examined in preneoplastic liver cell foci that expressed glutathione S-transferase placental form (GST-P) in early-stage tumor promotion over 6 weeks in a rat two-stage hepatocarcinogenesis model. Gene expression and concentrations of thiobarbituric acid-reactive substance (TBARS) in the liver were also analyzed. Cu-overloading alone exerted a weak promoting activity, which was enhanced by Fe-overloading. By Cu-overloading, GST-P(+) foci that co-expressed transferrin receptors or downregulated ceruloplasmin increased, suggesting preneoplastic lesion-specific enhancement of oxidative cellular stress. Cu-overloading also increased transcripts of antioxidant enzymes (Gstm3 and Gst Yc2 subunit), cell proliferation, and numbers of single liver cells expressing GST-P or heme oxygenase-1 (HO-1) in the liver, suggesting that oxidative stress induces single-cell toxicity, with the ensuing regeneration contributing to tumor promotion. Fe-overloading increased liver TBARS and HO-1-expressing Kupffer cells, the latter suggesting protection against inflammatory stimuli causing fluctuating proinflammatory cytokine mRNA levels. By co-overloading of Cu and Fe, Cu-overload-related single liver cell toxicity and regeneration increased, as did cytokine imbalances involving increased cyclooxygenase-2-producing Kupffer cells and accumulation of malondialdehyde within GST-P(+) foci. These results suggest an involvement of oxidative stress responses in Cu-induced tumor promotion and Fe-induced enhancement by increasing cytokine imbalances and GST-P(+) foci-specific lipid peroxidation.
    Chemico-biological interactions 03/2010; 185(3):189-201. DOI:10.1016/j.cbi.2010.03.023 · 2.98 Impact Factor
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    ABSTRACT: To investigate the modifying effect of enzymatically modified isoquercitrin (EMIQ) on hepatocellular tumor promotion induced by beta-naphthoflavone (BNF) treatment, male rats were administered a single intraperitoneal injection of N-diethylnitrosamine (DEN) and were fed a diet containing BNF (0.5%) for 6 weeks with or without EMIQ (0.2%) in the drinking water after DEN initiation. One week after the commencement of the administration of BNF, rats were subjected to a two-thirds partial hepatectomy. The number and area of GST-P positive foci, the number of COX2-positive cells and the area of elastica-van Gieson (EVG)-positive connective tissue fibers promoted by BNF were significantly suppressed by the administration of the antioxidant EMIQ. Real-time RT-PCR analysis revealed that EMIQ treatment decreased mRNA expression levels of Gstm1, Serpine1, Cox2 and Nfkbia and increased mRNA expression levels of Yc2 compared with those in the DEN-BNF group. These results suggest that co-administration of EMIQ suppresses the hepatocellular tumor-promoting activity of BNF in rats through the anti-inflammatory effects of EMIQ and restores the cellular redox balance altered by BNF.
    Toxicology 02/2010; 268(3):213-8. DOI:10.1016/j.tox.2009.12.019 · 3.75 Impact Factor
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    ABSTRACT: We report a rare case of benign sex cord-stromal tumor consisted largely of luteoma with minor portion of Sertoli cell tumor located at the position of the left ovary excision in an 11-year-old ovariectomized bitch. Granulosa cell component was lacking, and both luteal and Sertoli cell portions were entirely positive for inhibin alpha and neuron-specific enolase, whereas luteoma portion alone was positive for Wilms' tumor-1 (WT1), immunohistochemically. The results suggest that this tumor is a possible complication of incomplete ovarian excision at the time of ovariectomy and consisted of uncommon hybrid of luteal and Sertoli cells to be diagnosed as an unclassified sex cord-stromal tumor if applied in human cases. WT1-expression pattern suggested the signature of the difference in the phenotype of these cell types.
    Journal of Veterinary Medical Science 11/2009; 72(2):229-34. DOI:10.1292/jvms.09-0235 · 0.88 Impact Factor