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

DOI Web Site 被引用文献2件 参考文献42件
  • Watanabe Takashi
    Department of Chemistry and Biological Science, School of Science and Engineering, Aoyama Gakuin University
  • Tobe Kaori
    Department of Chemistry and Biological Science, School of Science and Engineering, Aoyama Gakuin University
  • Nakachi Yutaka
    Advanced Engineering Center, RIKEN
  • Kondoh Yasumitsu
    Advanced Engineering Center, RIKEN
  • Nakajima Madoka
    Genetic Toxicology Group, Biosafety Research Center, Foods, Drugs, and Pesticides
  • Hamada Shuichi
    Genetic Toxicology Group, Toxicology Division II, Kashima Laboratory, Mitsubishi Chemical Safety Institute LTD.
  • Namiki Chiaki
    Central Research Laboratory, SSP Co. Ltd.
  • Suzuki Takayoshi
    Division of Cellular & Gene Therapy Products, National Institute of Health Sciences
  • Maeda Satoru
    Department of Chemistry and Biological Science, School of Science and Engineering, Aoyama Gakuin University
  • Tadakuma Ayami
    Department of Chemistry and Biological Science, School of Science and Engineering, Aoyama Gakuin University
  • Sakurai Mikiya
    Department of Chemistry and Biological Science, School of Science and Engineering, Aoyama Gakuin University
  • Arai Yuko
    Department of Chemistry and Biological Science, School of Science and Engineering, Aoyama Gakuin University
  • 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
  • Tashiro Tomoko
    Department of Chemistry and Biological Science, School of Science and Engineering, Aoyama Gakuin University
  • Ito Hisashi
    Department of Chemistry and Biological Science, School of Science and Engineering, Aoyama Gakuin University
  • Inazumi Hiroshige
    Department of Information Technology, School of Science and Engineering, Aoyama Gakuin University
  • Sakaki Yoshiyuki
    Genetic Sciences Center, RIKEN
  • Tashiro Hideo
    Advanced Engineering Center, RIKEN
  • Furihata Chie
    Department of Chemistry and Biological Science, School of Science and Engineering, Aoyama Gakuin University

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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, 80 mg/kg bw), dipropylnitrosamine (DPN, 250 mg/kg bw), phenobarbital sodium (30 mg/kg bw) and ethanol (1000 mg/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 Mbd1, 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.<br>

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