Differential Gene Expression Induced by Two Genotoxic N-nitroso Carcinogens, Phenobarbital and Ethanol in Mouse Liver Examined with Oligonucleotide Microarray and Quantitative Real-time PCR

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概要

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• It is known that genotoxic N-nitroso carcinogens induce DNA damage in mouse liver within a few hours and induce mutations within 28 days after their administration. However, related-gene expression changes at these time points in liver were not fully elucidated. Differential gene expression induced by two genotoxic N-nitroso carcinogens in mouse liver was examined 4 h and 28 days after their administration with in-house oligonucleotide microarray (268 genes) and quantitative real-time PCR, and compared to that of a non-genotoxic carcinogen and a non-carcinogenic toxin. Diethylnitrosamine (DEN, 80mg/kg bw), dipropylnitrosamine (DPN, 250mg/kg bw), phenobarbital sodium (30mg/kg bw) and ethanol (1000mg/kg bw) were injected intraperitoneally into groups of male 9-week-old B6C3F1 mice and liver was dissected after 4 h and 28 days. mRNA from pooled livers was reverse-transcribed to cDNA, and Cy3- and Cy5-labeled cDNA was competitively hybridized with in-house made microarray, scanned and analyzed ; additionally, quantitative real-time PCR was performed for selected genes. Differential gene expression between two genotoxic N-nitroso carcinogens and phenobarbital and ethanol was observed in 11 genes 4 h after administration, including seven tumor suppressor p53 target genes, viz. c-Jun, Ccng1, Mdm2, p21, Bax, Hsp27 and Snk ; the other genes were Mbd 1, Hmox-1, Ccnf and Rad52. However, only some degree of differential gene expression of p21, Ccng1 and Snk was observed 28 days after administration ; no other differentially-expressed genes were evident. The present results suggest that DEN and DPN induce differential gene expression in p53 target genes in liver within a few hours after administration and that these acute responses remained only partially in liver after 28 days.

• 日本環境変異原学会の論文
• 2007-08-31

著者

• Watanabe Takashi

  Department of Chemistry, Graduate School of Science, Kyoto University

• FURIHATA Chie

  Department of Molecular Oncology, Institute of Medical Science, University of Tokyo

• Suzuki Takayoshi

  Division of Cellular and Gene Therapy Products, National Institute of Health Sciences

• ITO Hisashi

  Department of Chemistry, Faculty of Science and Engineering, Aoyama Gakuin University

• SAKURAI Mikiya

  Department of Chemical Engineering, Tokyo Institute of Technology

• Sakurai Mikiya

  Department Of Chemistry And Biological Science

• Sakurai Mikiya

  Department Of Chemical Engineering Tokyo Institute Of Technology

• Tashiro Tomoko

  Department Of Chemistry And Biological Science School Of Science And Engineering Aoyama Gakuin Unive

• Tashiro Tomoko

  Department Of Cellular And Molecular Neurobiology Gunma University School Of Medicine

• Sakaki Yoshiyuki

  Genetic Sciences Center Riken

• Arai Yuko

  Department Of Ophthalmology Hirosaki City Hospital

• Arai Yuko

  Department Of Chemistry And Biological Science

• Tashiro Hideo

  Probing Technology Laboratory Institute Of Physical And Chemical Research (riken)

• Hamada Shuichi

  Genetic Toxicology Group Toxicology Division Ii Kashima Laboratory Mitsubishi Chemical Safety Instit

• Nakachi Yutaka

  Advanced Engineering Center

• NAKAJIMA Madoka

  Genetic Toxicology Group, Biosafety Research Center, Foods, Drugs and Pesticides

• TASHIRO Hideo

  Advanced Engineering Center, RIKEN

• Tobe Kaori

  Department of Chemistry and Biological Science

• Kondoh Yasumitsu

  Advanced Engineering Center

• Namiki Chiaki

  Central Research Laboratory, SSP Co. Ltd.

• Maeda Satoru

  Department of Chemistry and Biological Science

• Tadakuma Ayami

  Department of Chemistry and Biological Science

• Hyogo Atsushi

  Laboratory Animal Science and Toxicology Laboratories, Sankyo Co. Ltd.

• Hoshino Masako

  Department of Information Technology, School of Science and Engineering, Aoyama Gakuin University

• Inazumi Hiroshige

  Department of Information Technology, School of Science and Engineering, Aoyama Gakuin University

• Namiki Chiaki

  Central Research Laboratory Ssp Co. Ltd.

• Hyogo Atsushi

  Laboratory Animal Science And Toxicology Laboratories Sankyo Co. Ltd.

• Hoshino Masako

  Department Of Information Technology School Of Science And Engineering Aoyama Gakuin University

• Nakajima Madoka

  Genetic Toxicology Group Biosafety Research Center Foods Drugs And Pesticides

• Arai Yuko

  Department Of Cell Biology National Institute For Basic Biology

• Furihata Chie

  Department Of Chemistry And Biological Science School Of Science And Engineering Aoyama Gakuin Unive

• KONDOH Yasumitsu

  Probing Technology Laboratory, Institute of Physical and Chemical Research (RIKEN)

• Kondoh Yasumitsu

  Probing Technology Laboratory Institute Of Physical And Chemical Research (riken)

• Inazumi Hiroshige

  Department Of Information Technology School Of Science And Engineering Aoyama Gakuin University

• Ito Hisashi

  Department Of Chemistry And Biological Science

• Suzuki Takayoshi

  Division Of Cellular & Gene Therapy Products National Institute Of Health Sciences

• Watanabe Takashi

  Department Of Chemistry And Materials Science Tokyo Institute Of Technology

• Watanabe Takashi

  Department Of Cardiothoracic Surgery Nagoya University School Of Medicine

• Watanabe Takashi

  Department Of Applied Physics Tohoku University

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