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http://dx.doi.org/10.5487/TR.2007.23.3.231

Establishment of Reporter Cell Lines that Monitor Activities of Hypoxia Inducible Factor-1, P53 and Nur77 for Assessment of Carcinogenicity  

Hong, Il (College of Pharmacy, Seoul National University)
Seo, Hee-Won (College of Pharmacy, Seoul National University)
Lee, Min-Ho (College of Pharmacy, Seoul National University)
Kim, Ji-Won (College of Pharmacy, Seoul National University)
Chung, Jin-Ho (College of Pharmacy, Seoul National University)
Lee, Byung-Hoon (College of Pharmacy, Seoul National University)
Lee, Mi-Ock (College of Pharmacy, Seoul National University)
Publication Information
Toxicological Research / v.23, no.3, 2007 , pp. 231-238 More about this Journal
Abstract
Evaluation of potentials of chemicals to alter expression of genes that are involved in carcinogenesis may serve useful tools in toxicological research. In this investigation, we developed reporter cell lines that expressed luciferase in response to transactivation of hypoxia inducible factor-1, P53 tumor suppressor and Nur77 of which roles have been well established in cancer development and progression. Whereas these reporter cell lines displayed low constitutive backgrounds, the reporter activities were significantly enhanced in response to $desferriosamine/CoCl_2$, adriamycin or 6-mercaptopurine, which are hypoxia mimicking chemicals, P53 activator or Nur77 inducer, respectively. The activation of the reporter was time- and dose-dependent. Known tumor initiators and promoters, such as phorbol 12-myristate 13-acetate and phorbol 12, 13-dicaprinate induced the reporter activity at as low as 10nM in these stable cell lines. Further, known anti-tumor promoters, such as ascorbic acid and ${\beta}-carotene$ repressed the reporter activities. These results indicate that our stable reporter cell lines could serve as a useful system for rapid assessment of carcinogenicity of toxic chemicals.
Keywords
Reporter cell line; HIF-1; P53; Nur77; Carcinogenicity.;
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