Synergism between 2,3,7,8-tetrachlorodibenzo-p-dioxin and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone on lung tumor incidence in mice

Ying Jan Wang, Han Chang, Yu Chun Kuo, Chien Kai Wang, Shih He Siao, Louis W. Chang, Pinpin Lin

研究成果: Article同行評審

6 引文 斯高帕斯(Scopus)

摘要

Although 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is classified as a human carcinogen, TCDD only induced oxidative DNA damages. In our present study, we combined TCDD with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) to investigate their tumorigenic effects on lung tumor formation in A/J mice. Application of NNK at a tumorigenic dose (2. mg/mouse) induced lung adenoma in both male and female A/J mice. Neither application of NNK at a non-tumorigenic dose (1. mg/mouse) nor repeated application of TCDD alone increased tumor incidence. Following the single injection of NNK at a non-tumorigenic dose (1. mg/mouse), repeated application of TCDD significantly increased the lung tumor incidence in female, but not in male, A/J mice 24 weeks later. Utilizing the real-time RT-PCR array, we found that P16 mRNA was significantly reduced in female lung, but not male lung, of NNK/TCDD co-treated A/J mice. With immunohistochemical staining, we confirmed that nuclear P16 protein was reduced in the lungs of NNK/TCDD co-treated female mice. These data suggest that P16 reduction at least partially contributed to synergistic effects of TCDD in lung tumorigenesis.

原文English
頁(從 - 到)869-875
頁數7
期刊Journal of Hazardous Materials
186
發行號1
DOIs
出版狀態Published - 2011 2月 15

All Science Journal Classification (ASJC) codes

  • 環境工程
  • 環境化學
  • 廢物管理和處置
  • 污染
  • 健康、毒理學和誘變

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