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

Genes and Environment

Satoru Maeda⁵  Yuko Arai⁵  Atsushi Hyogo⁴  Takashi Watanabe⁵  Yoshiyuki Sakaki⁸  Chiaki Namiki²  Madoka Nakajima⁹  Ayami Tadakuma⁵  Hiroshige Inazumi⁷  Yasumitsu Kondoh³  Masako Hoshino⁷  Shuichi Hamada¹  Takayoshi Suzuki⁶  Hisashi Ito⁵  Mikiya Sakurai⁵  Tomoko Tashiro⁵  Kaori Tobe⁵  Chie Furihata⁵  Yutaka Nakachi³  Hideo Tashiro³ 

[1] Genetic Toxicology Group, Toxicology Division II, Kashima Laboratory, Mitsubishi Chemical Safety Institute LTD.;Central Research Laboratory, SSP Co. Ltd.;Advanced Engineering Center, RIKEN;Laboratory Animal Science and Toxicology Laboratories, Sankyo Co. Ltd.;Department of Chemistry and Biological Science, School of Science and Engineering, Aoyama Gakuin University;Division of Cellular & Gene Therapy Products, National Institute of Health Sciences;Department of Information Technology, School of Science and Engineering, Aoyama Gakuin University;Genetic Sciences Center, RIKEN;Genetic Toxicology Group, Biosafety Research Center, Foods, Drugs, and Pesticides

关键词: quantitative real-time PCR;    oligonucleotide microarray;    toxicogenomics;    genotoxic carcinogens;    non-genotoxic tumor promoter;   

DOI  :  10.3123/jemsge.29.115

学科分类：分子生物学，细胞生物学和基因

来源: Japanese Environmental Mutagen Society / Nihon Kankyo Hen igen Gakkai

【 摘 要 】

References(28)Cited-By(7)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.

【 授权许可】

Unknown