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Hepatocarcinogenic susceptibility of rasH2 mice to troglitazone in a two-stage hepatocarcinogenesis model

  • Genotoxicity and Carcinogenicity
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Abstract

Six-week-old rasH2 mice were injected intraperitoneally with N-diethylnitrosamine (DEN) after partial hepatectomy and administrated 0 or 6,000 ppm troglitazone (TRG) for 10 weeks. Relative liver weight of females increased significantly in the DEN + TRG group compared to the DEN-alone group. The numbers of γ-glutamyltranspeptidase- and proliferating cell nuclear antigen (PCNA)-positive cells tended to increase in both the sexes in the DEN + TRG group; however, these changes were not significantly different from those in the DEN-alone group. Levels of gene expressions for vascular endothelial growth factor (VEGF) and VEGFB (related to angiogenesis), tropomyosin 1 (Tpm1) and transforming growth factor-β (related to ras/MAPK cascade activation), and PCNA (related to cell proliferation) in females were significantly higher in the DEN + TRG than in the untreated control group but not in the DEN-alone group. Only Tpm1 gene had significantly higher expression in the DEN + TRG group than in the DEN-alone group. These results suggest that rasH2 mice are not susceptible to TRG in a two-stage hepatocarcinogenesis model.

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Authors and Affiliations

  1. Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo, 183-8509, Japan

    Meilan Jin, Yukie Saekusa, Yasuaki Dewa, Jihei Nishimura, Sayaka Matsumoto, Makoto Shibutani & Kunitoshi Mitsumori

  2. Department of Applied Biological Science, United Graduate School of Agricultural Sciences, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo, 183-8509, Japan

    Meilan Jin & Keiji Hasumi

  3. Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu-shi, Gifu, 501-1193, Japan

    Yukie Saekusa, Yasuaki Dewa, Jihei Nishimura & Sayaka Matsumoto

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  1. Meilan Jin
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  2. Yukie Saekusa
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  3. Yasuaki Dewa
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  4. Jihei Nishimura
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  7. Keiji Hasumi
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  8. Kunitoshi Mitsumori
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Correspondence to Meilan Jin.

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Jin, M., Saekusa, Y., Dewa, Y. et al. Hepatocarcinogenic susceptibility of rasH2 mice to troglitazone in a two-stage hepatocarcinogenesis model. Arch Toxicol 83, 173–181 (2009). https://doi.org/10.1007/s00204-008-0335-5

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  • DOI: https://doi.org/10.1007/s00204-008-0335-5

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