title: Detection of the onset of ischemia and carcinogenesis by hypoxia-inducible transcription factor-based in vivo bioluminescence imaging.
abstract: 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.
authors.affiliation: Department of Biomolecular Engineering, Tokyo Institute of Technology Graduate School of Bioscience and Biotechnology, Nagatsuta-cho, Midori-ku, Yokohama, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kadonosono
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kuchimaru
authors.forename: Shuichi
authors.initials: S
authors.lastname: Yamada
authors.forename: Yumi
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Murakami
authors.forename: Taeko
authors.initials: T
authors.lastname: Tani
authors.forename: Hitomi
authors.initials: H
authors.lastname: Watanabe
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Tanaka
authors.forename: Kiichi
authors.initials: K
authors.lastname: Hirota
authors.forename: Masahiro
authors.initials: M
authors.lastname: Inoue
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Tsukamoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Toyoda
authors.forename: Koji
authors.initials: K
authors.lastname: Urano
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Machida
authors.forename: Tomoo
authors.initials: T
authors.lastname: Eto
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Ogura
authors.forename: Hideki
authors.initials: H
authors.lastname: Tsutsumi
authors.forename: Mamoru
authors.initials: M
authors.lastname: Ito
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hiraoka
authors.forename: Gen
authors.initials: G
authors.lastname: Kondoh
authors.forename: Shinae
authors.initials: S
authors.lastname: Kizaka-Kondoh
mesh_terms: D000477:Alkylating Agents / Q000633:toxicity; D000818:Animals; D015139:Blotting, Southern; D015197:Carcinogenicity Tests / Q000379:methods*; D005260:Female; D011905:Genes, ras; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism*; D007091:Image Processing, Computer-Assisted; D007511:Ischemia / Q000139:chemically induced / Q000175:diagnosis* / Q000378:metabolism; D008163:Luminescent Measurements; D008164:Luminescent Proteins / Q000378:metabolism*; D008297:Male; D008770:Methylnitrosourea / Q000633:toxicity; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000175:diagnosis* / Q000378:metabolism; D010212:Papilloma / Q000139:chemically induced / Q000175:diagnosis* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000477:Alkylating Agents; D051793:Hypoxia-Inducible Factor 1; D008164:Luminescent Proteins; D012333:RNA, Messenger; D008770:Methylnitrosourea
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