Detection of the onset of ischemia and carcinogenesis by hypoxia-inducible transcription factor-based in vivo bioluminescence imaging.
An animal model for the early detection of common fatal diseases such as ischemic diseases and cancer is desirable for the development of new drugs and treatment strategies. Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that regulates oxygen homeostasis and plays key roles in a number...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2011-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3213102?pdf=render |
| _version_ | 1818327542071820288 |
|---|---|
| author | Tetsuya Kadonosono Takahiro Kuchimaru Shuichi Yamada Yumi Takahashi Atsushi Murakami Taeko Tani Hitomi Watanabe Tomoharu Tanaka Kiichi Hirota Masahiro Inoue Tetsuya Tsukamoto Takeshi Toyoda Koji Urano Kazuhiko Machida Tomoo Eto Tomoyuki Ogura Hideki Tsutsumi Mamoru Ito Masahiro Hiraoka Gen Kondoh Shinae Kizaka-Kondoh |
| author_facet | Tetsuya Kadonosono Takahiro Kuchimaru Shuichi Yamada Yumi Takahashi Atsushi Murakami Taeko Tani Hitomi Watanabe Tomoharu Tanaka Kiichi Hirota Masahiro Inoue Tetsuya Tsukamoto Takeshi Toyoda Koji Urano Kazuhiko Machida Tomoo Eto Tomoyuki Ogura Hideki Tsutsumi Mamoru Ito Masahiro Hiraoka Gen Kondoh Shinae Kizaka-Kondoh |
| author_sort | Tetsuya Kadonosono |
| collection | DOAJ |
| description | An animal model for the early detection of common fatal diseases such as ischemic diseases and cancer is desirable for the development of new drugs and treatment strategies. Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that regulates oxygen homeostasis and plays key roles in a number of diseases, including cancer. Here, we established transgenic (Tg) mice that carry HRE/ODD-luciferase (HOL) gene, which generates bioluminescence in an HIF-1-dependent manner and was successfully used in this study to monitor HIF-1 activity in ischemic tissues. To monitor carcinogenesis in vivo, we mated HOL mice with rasH2 Tg mice, which are highly sensitive to carcinogens and are used for short-term carcinogenicity assessments. After rasH2-HOL Tg mice were treated with N-methyl-N-nitrosourea, bioluminescence was detected noninvasively as early as 9 weeks in tissues that contained papillomas and malignant lesions. These results suggest that the Tg mouse lines we established hold significant potential for monitoring the early onset of both ischemia and carcinogenesis and that these lines will be useful for screening chemicals for carcinogenic potential. |
| first_indexed | 2024-12-13T12:17:55Z |
| format | Article |
| id | doaj.art-95bac02f1942438a9e284116cc01bc6c |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T12:17:55Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-95bac02f1942438a9e284116cc01bc6c2022-12-21T23:46:40ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-01611e2664010.1371/journal.pone.0026640Detection of the onset of ischemia and carcinogenesis by hypoxia-inducible transcription factor-based in vivo bioluminescence imaging.Tetsuya KadonosonoTakahiro KuchimaruShuichi YamadaYumi TakahashiAtsushi MurakamiTaeko TaniHitomi WatanabeTomoharu TanakaKiichi HirotaMasahiro InoueTetsuya TsukamotoTakeshi ToyodaKoji UranoKazuhiko MachidaTomoo EtoTomoyuki OguraHideki TsutsumiMamoru ItoMasahiro HiraokaGen KondohShinae Kizaka-KondohAn animal model for the early detection of common fatal diseases such as ischemic diseases and cancer is desirable for the development of new drugs and treatment strategies. Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that regulates oxygen homeostasis and plays key roles in a number of diseases, including cancer. Here, we established transgenic (Tg) mice that carry HRE/ODD-luciferase (HOL) gene, which generates bioluminescence in an HIF-1-dependent manner and was successfully used in this study to monitor HIF-1 activity in ischemic tissues. To monitor carcinogenesis in vivo, we mated HOL mice with rasH2 Tg mice, which are highly sensitive to carcinogens and are used for short-term carcinogenicity assessments. After rasH2-HOL Tg mice were treated with N-methyl-N-nitrosourea, bioluminescence was detected noninvasively as early as 9 weeks in tissues that contained papillomas and malignant lesions. These results suggest that the Tg mouse lines we established hold significant potential for monitoring the early onset of both ischemia and carcinogenesis and that these lines will be useful for screening chemicals for carcinogenic potential.http://europepmc.org/articles/PMC3213102?pdf=render |
| spellingShingle | Tetsuya Kadonosono Takahiro Kuchimaru Shuichi Yamada Yumi Takahashi Atsushi Murakami Taeko Tani Hitomi Watanabe Tomoharu Tanaka Kiichi Hirota Masahiro Inoue Tetsuya Tsukamoto Takeshi Toyoda Koji Urano Kazuhiko Machida Tomoo Eto Tomoyuki Ogura Hideki Tsutsumi Mamoru Ito Masahiro Hiraoka Gen Kondoh Shinae Kizaka-Kondoh Detection of the onset of ischemia and carcinogenesis by hypoxia-inducible transcription factor-based in vivo bioluminescence imaging. PLoS ONE |
| title | Detection of the onset of ischemia and carcinogenesis by hypoxia-inducible transcription factor-based in vivo bioluminescence imaging. |
| title_full | Detection of the onset of ischemia and carcinogenesis by hypoxia-inducible transcription factor-based in vivo bioluminescence imaging. |
| title_fullStr | Detection of the onset of ischemia and carcinogenesis by hypoxia-inducible transcription factor-based in vivo bioluminescence imaging. |
| title_full_unstemmed | Detection of the onset of ischemia and carcinogenesis by hypoxia-inducible transcription factor-based in vivo bioluminescence imaging. |
| title_short | Detection of the onset of ischemia and carcinogenesis by hypoxia-inducible transcription factor-based in vivo bioluminescence imaging. |
| title_sort | detection of the onset of ischemia and carcinogenesis by hypoxia inducible transcription factor based in vivo bioluminescence imaging |
| url | http://europepmc.org/articles/PMC3213102?pdf=render |
| work_keys_str_mv | AT tetsuyakadonosono detectionoftheonsetofischemiaandcarcinogenesisbyhypoxiainducibletranscriptionfactorbasedinvivobioluminescenceimaging AT takahirokuchimaru detectionoftheonsetofischemiaandcarcinogenesisbyhypoxiainducibletranscriptionfactorbasedinvivobioluminescenceimaging AT shuichiyamada detectionoftheonsetofischemiaandcarcinogenesisbyhypoxiainducibletranscriptionfactorbasedinvivobioluminescenceimaging AT yumitakahashi detectionoftheonsetofischemiaandcarcinogenesisbyhypoxiainducibletranscriptionfactorbasedinvivobioluminescenceimaging AT atsushimurakami detectionoftheonsetofischemiaandcarcinogenesisbyhypoxiainducibletranscriptionfactorbasedinvivobioluminescenceimaging AT taekotani detectionoftheonsetofischemiaandcarcinogenesisbyhypoxiainducibletranscriptionfactorbasedinvivobioluminescenceimaging AT hitomiwatanabe detectionoftheonsetofischemiaandcarcinogenesisbyhypoxiainducibletranscriptionfactorbasedinvivobioluminescenceimaging AT tomoharutanaka detectionoftheonsetofischemiaandcarcinogenesisbyhypoxiainducibletranscriptionfactorbasedinvivobioluminescenceimaging AT kiichihirota detectionoftheonsetofischemiaandcarcinogenesisbyhypoxiainducibletranscriptionfactorbasedinvivobioluminescenceimaging AT masahiroinoue detectionoftheonsetofischemiaandcarcinogenesisbyhypoxiainducibletranscriptionfactorbasedinvivobioluminescenceimaging AT tetsuyatsukamoto detectionoftheonsetofischemiaandcarcinogenesisbyhypoxiainducibletranscriptionfactorbasedinvivobioluminescenceimaging AT takeshitoyoda detectionoftheonsetofischemiaandcarcinogenesisbyhypoxiainducibletranscriptionfactorbasedinvivobioluminescenceimaging AT kojiurano detectionoftheonsetofischemiaandcarcinogenesisbyhypoxiainducibletranscriptionfactorbasedinvivobioluminescenceimaging AT kazuhikomachida detectionoftheonsetofischemiaandcarcinogenesisbyhypoxiainducibletranscriptionfactorbasedinvivobioluminescenceimaging AT tomooeto detectionoftheonsetofischemiaandcarcinogenesisbyhypoxiainducibletranscriptionfactorbasedinvivobioluminescenceimaging AT tomoyukiogura detectionoftheonsetofischemiaandcarcinogenesisbyhypoxiainducibletranscriptionfactorbasedinvivobioluminescenceimaging AT hidekitsutsumi detectionoftheonsetofischemiaandcarcinogenesisbyhypoxiainducibletranscriptionfactorbasedinvivobioluminescenceimaging AT mamoruito detectionoftheonsetofischemiaandcarcinogenesisbyhypoxiainducibletranscriptionfactorbasedinvivobioluminescenceimaging AT masahirohiraoka detectionoftheonsetofischemiaandcarcinogenesisbyhypoxiainducibletranscriptionfactorbasedinvivobioluminescenceimaging AT genkondoh detectionoftheonsetofischemiaandcarcinogenesisbyhypoxiainducibletranscriptionfactorbasedinvivobioluminescenceimaging AT shinaekizakakondoh detectionoftheonsetofischemiaandcarcinogenesisbyhypoxiainducibletranscriptionfactorbasedinvivobioluminescenceimaging |