저산소유도인자 HIF-1, 암 억제인자 P53과 고아 핵수용체 Nur77의 발현을 지표로 하는 발암독성예측 세포주의 개발

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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/CoCl₂, 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 10 nM in these stable cell lines. Further, known anti-tumor promoters, such as ascorbic acid and β-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.