Discrimination of Carcinogens by Hepatic Transcript Profiling in Rats following 28-day Administration
This study aimed at discriminating carcinogens on the basis of hepatic transcript profiling in the rats administrated with a variety of carcinogens and non-carcinogens. We conducted 28-day toxicity tests in male F344 rats with 47 carcinogens and 26 non-carcinogens, and then investigated periodically...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2009-01-01
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| Series: | Cancer Informatics |
| Online Access: | https://doi.org/10.4137/CIN.S3229 |
| _version_ | 1818807535366307840 |
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| author | Hiroshi Matsumoto Yoshikuni Yakabe Koichi Saito Kayo Sumida Masaru Sekijima Koji Nakayama Hideki Miyaura Fumiyo Saito Masanori Otsuka Tomoyuki Shirai |
| author_facet | Hiroshi Matsumoto Yoshikuni Yakabe Koichi Saito Kayo Sumida Masaru Sekijima Koji Nakayama Hideki Miyaura Fumiyo Saito Masanori Otsuka Tomoyuki Shirai |
| author_sort | Hiroshi Matsumoto |
| collection | DOAJ |
| description | This study aimed at discriminating carcinogens on the basis of hepatic transcript profiling in the rats administrated with a variety of carcinogens and non-carcinogens. We conducted 28-day toxicity tests in male F344 rats with 47 carcinogens and 26 non-carcinogens, and then investigated periodically the hepatic gene expression profiles using custom microarrays. By hierarchical cluster analysis based on significantly altered genes, carcinogens were clustered into three major groups (Group 1 to 3). The formation of these groups was not affected by the gene sets used as well as the administration period, indicating that the grouping of carcinogens was universal independent of the conditions of both statistical analysis and toxicity testing. Seventeen carcinogens belonging to Group 1 were composed of mainly rat hepatocarcinogens, most of them being mutagenic ones. Group 2 was formed by three subgroups, which were composed of 23 carcinogens exhibiting distinct properties in terms of genotoxicity and target tissues, namely nonmutagenic hepatocarcinogens, and mutagenic and nonmutagenic carcinogens both of which are targeted to other tissues. Group 3 contained 6 carcinogens including 4 estrogenic substances, implying the group of estrogenic carcinogens. Gene network analyses revealed that the significantly altered genes in Group 1 included Bax, Tnfrsf6, Btg2, Mgmt and Abcb1b, suggesting that p53-mediated signaling pathway involved in early pathologic alterations associated with preceding mutagenic carcinogenesis. Thus, the common transcriptional signatures for each group might reflect the early molecular events of carcinogenesis and hence would enable us to identify the biomarker genes, and then to develop a new assay for carcinogenesis prediction. |
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| format | Article |
| id | doaj.art-86eef623642042ad81260855bdc35323 |
| institution | Directory Open Access Journal |
| issn | 1176-9351 |
| language | English |
| last_indexed | 2024-12-18T19:27:12Z |
| publishDate | 2009-01-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cancer Informatics |
| spelling | doaj.art-86eef623642042ad81260855bdc353232022-12-21T20:55:50ZengSAGE PublishingCancer Informatics1176-93512009-01-01710.4137/CIN.S3229Discrimination of Carcinogens by Hepatic Transcript Profiling in Rats following 28-day AdministrationHiroshi Matsumoto0Yoshikuni Yakabe1Koichi Saito2Kayo Sumida3Masaru Sekijima4Koji Nakayama5Hideki Miyaura6Fumiyo Saito7Masanori Otsuka8Tomoyuki Shirai9Chemical Assessment Center, Chemicals evaluation and research Institute, Japan (CERI), 1600, Shimo-Takano, Sugito-Machi, Kitakatsushika-gun, Saitama 345–0043, Japan.Chemical Assessment Center, Chemicals evaluation and research Institute, Japan (CERI), 1600, Shimo-Takano, Sugito-Machi, Kitakatsushika-gun, Saitama 345–0043, Japan.Sumitomo Chemical Co., Ltd., Osaka, Japan.Sumitomo Chemical Co., Ltd., Osaka, Japan.Mitsubishi Chemical Safety Institute Ltd., Ibaraki, Japan.Mitsubishi Chemical Safety Institute Ltd., Ibaraki, Japan.Chemical Assessment Center, Chemicals evaluation and research Institute, Japan (CERI), 1600, Shimo-Takano, Sugito-Machi, Kitakatsushika-gun, Saitama 345–0043, Japan.Chemical Assessment Center, Chemicals evaluation and research Institute, Japan (CERI), 1600, Shimo-Takano, Sugito-Machi, Kitakatsushika-gun, Saitama 345–0043, Japan.Chemical Assessment Center, Chemicals evaluation and research Institute, Japan (CERI), 1600, Shimo-Takano, Sugito-Machi, Kitakatsushika-gun, Saitama 345–0043, Japan.Graduate school of Medical Sciences, Nagoya City University, Nagoya, Japan.This study aimed at discriminating carcinogens on the basis of hepatic transcript profiling in the rats administrated with a variety of carcinogens and non-carcinogens. We conducted 28-day toxicity tests in male F344 rats with 47 carcinogens and 26 non-carcinogens, and then investigated periodically the hepatic gene expression profiles using custom microarrays. By hierarchical cluster analysis based on significantly altered genes, carcinogens were clustered into three major groups (Group 1 to 3). The formation of these groups was not affected by the gene sets used as well as the administration period, indicating that the grouping of carcinogens was universal independent of the conditions of both statistical analysis and toxicity testing. Seventeen carcinogens belonging to Group 1 were composed of mainly rat hepatocarcinogens, most of them being mutagenic ones. Group 2 was formed by three subgroups, which were composed of 23 carcinogens exhibiting distinct properties in terms of genotoxicity and target tissues, namely nonmutagenic hepatocarcinogens, and mutagenic and nonmutagenic carcinogens both of which are targeted to other tissues. Group 3 contained 6 carcinogens including 4 estrogenic substances, implying the group of estrogenic carcinogens. Gene network analyses revealed that the significantly altered genes in Group 1 included Bax, Tnfrsf6, Btg2, Mgmt and Abcb1b, suggesting that p53-mediated signaling pathway involved in early pathologic alterations associated with preceding mutagenic carcinogenesis. Thus, the common transcriptional signatures for each group might reflect the early molecular events of carcinogenesis and hence would enable us to identify the biomarker genes, and then to develop a new assay for carcinogenesis prediction.https://doi.org/10.4137/CIN.S3229 |
| spellingShingle | Hiroshi Matsumoto Yoshikuni Yakabe Koichi Saito Kayo Sumida Masaru Sekijima Koji Nakayama Hideki Miyaura Fumiyo Saito Masanori Otsuka Tomoyuki Shirai Discrimination of Carcinogens by Hepatic Transcript Profiling in Rats following 28-day Administration Cancer Informatics |
| title | Discrimination of Carcinogens by Hepatic Transcript Profiling in Rats following 28-day Administration |
| title_full | Discrimination of Carcinogens by Hepatic Transcript Profiling in Rats following 28-day Administration |
| title_fullStr | Discrimination of Carcinogens by Hepatic Transcript Profiling in Rats following 28-day Administration |
| title_full_unstemmed | Discrimination of Carcinogens by Hepatic Transcript Profiling in Rats following 28-day Administration |
| title_short | Discrimination of Carcinogens by Hepatic Transcript Profiling in Rats following 28-day Administration |
| title_sort | discrimination of carcinogens by hepatic transcript profiling in rats following 28 day administration |
| url | https://doi.org/10.4137/CIN.S3229 |
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