YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Effects of Arsenic Trioxide on Cell Cycle Related Proteins (Cyclin D1, p21, p27) Expression During Urethane-induced Lung Carcinogenesis in Mice

Urethane으로 유발된 생쥐 폐샘암종 발생과정에서 세포주기 관련인자(Cyclin D1, p21, and p27)에 대한 비소의 효과

  • Yim Sung-Hyuk (Department of Pharmacology, School of Medicine, Chung-Ang University) ;
  • Jeong Ji-Hoon (Department of Pharmacology, School of Medicine, Chung-Ang University) ;
  • Gyeon Jong-Man (Department of Pathology, School of Medicine, Chung-Ang University) ;
  • Park Eon-Sub (Department of Pathology, School of Medicine, Chung-Ang University)
  • 임성혁 (중앙대학교 의과대학 약리학교실) ;
  • 정지훈 (중앙대학교 의과대학 약리학교실) ;
  • 견종만 (중앙대학교 의과대학 병리학교실) ;
  • 박언섭 (중앙대학교 의과대학 병리학교실)
  • Published : 2006.04.01
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Abstract

The present study investigated an effect of arsenic trioxide on the urethane-induced lung carcinogenesis in mice. To understand its carcinogenesis, we examined proliferating cell nuclear antigen (PCNA), apoptotic index as well as cell cycle-related proteins (cyclin D1, p21, and p27). Urethane was injected intraperitoneally in ICR mice, and then they were sacrificed at 5, 15, or 25 weeks following treatment of arsenic trioxide. Arsenic trioxide was given with tap water at a concentration of 1 mg/l (low-dose) and 5mg/1 (high-dose) for 25 weeks. During the carcinogenesis, sequential histological changes from hyperplasia to adenomas, and ultimately to overt carcinomas were noted. The development of hyperplasias, adenomas, and carcinomas in the lung were slightly increased by the treatment of low-dose arsenic trioxide. However, there is no correlation between dose and tumor multiplicity. The administration of low-dose arsenic trioxide, significantly increased the tumor size. The proliferative index observed on 5 weeks after significantly increased. Cyclin D1 and p21 protein, cell cycle related proteins, were more significantly increased in hyperplasia and adenoma in low dose arsenic treated group than urethane alone group. The p27 protein expression did not show any significantly changes with arsenic treated or untreated group. Low dose exposure to arsenic trioxide resulted in increased expression of cyclin D1 and p21 protein. The present results indicate that low-dose treatment of arsenic trioxide, but not high dose of it, partly modulate the cellular proliferation, cyclin D1, and p21 protein expression, and that this effect may contribute to accelerated development of lung adenocarcinomas in urethane-induced mice.

Keywords

References

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