Synergistic Effects of 2,3,7,8-Tetrachlorodibenzo-p-dioxin and N-nitrosodiethylamine on Cell Malignant Transformation  

作　　者：ZHANG Lei ZHAO Rui YE Shu Qing ZHOU Ling WU Yong Ning ZENG Yi 

机构地区：[1]Key Laboratory of Food Safety Risk Assessment,Ministry of Health,China National Center for Food Safety Risk Assessment [2]College of Life Science and Bio-engineering,Beijing University of Technology [3]National Institute for Viral Disease Control and Prevention,Chinese Center for Disease Control and Prevention

出　　处：《Biomedical and Environmental Sciences》2013年第5期323-330,共8页生物医学与环境科学（英文版）

基　　金：supported by the National Key Technology R&D Program (No. 2006BAI19B03);the National Key Basic Research Program of China (973 program No: 2012CB720804)

摘　　要：Objective The present paper aims to investigate the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin （TCDD） and N-nitrosodiethylamine （DEN） on tumorigenesis and its potential mechanism. Methods The potentials of TCDD and DEN in separation or in combination to induce malignant transformation were tested in Balb/c 3T3 cells by using a cell transformation assay method. The possible mechanism of observed effects was studied further by adding α-naphthoflavone （α-NF）, a competitive binding agent of TCDD, to the Aryl hydrocarbon receptor （AhR） pathway. The mRNA expressions of Cyp1a1 and Cyp2a5 gene in Balb/c 3T3 cells treated by DEN and TCDD in separation or in combination with or without presence of α-NF were measured with fluorescence quantification RT-PCR technique. Results The cell transformation frequency （TF） was significantly higher in case of induction with TCDD in combination with DEN, as compared to that with either TCDD or DEN alone. These effects were not inhibited via α-NF. The mRNA expression levels of both Cyp1a1 and Cyp2a5 were enhanced by TCDD treatment alone, but this inducible effect was blocked in cells treated by TCDD and DEN in combination. Conclusion TCDD and DEN had a significant synergistic effect on tumorigenesis when they were used in combination. AhR pathway may not be the key mechanism of this synergistic effect. Thus, it is necessary to further test the potential mechanism involved in cancer development.Objective The present paper aims to investigate the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin （TCDD） and N-nitrosodiethylamine （DEN） on tumorigenesis and its potential mechanism. Methods The potentials of TCDD and DEN in separation or in combination to induce malignant transformation were tested in Balb/c 3T3 cells by using a cell transformation assay method. The possible mechanism of observed effects was studied further by adding α-naphthoflavone （α-NF）, a competitive binding agent of TCDD, to the Aryl hydrocarbon receptor （AhR） pathway. The mRNA expressions of Cyp1a1 and Cyp2a5 gene in Balb/c 3T3 cells treated by DEN and TCDD in separation or in combination with or without presence of α-NF were measured with fluorescence quantification RT-PCR technique. Results The cell transformation frequency （TF） was significantly higher in case of induction with TCDD in combination with DEN, as compared to that with either TCDD or DEN alone. These effects were not inhibited via α-NF. The mRNA expression levels of both Cyp1a1 and Cyp2a5 were enhanced by TCDD treatment alone, but this inducible effect was blocked in cells treated by TCDD and DEN in combination. Conclusion TCDD and DEN had a significant synergistic effect on tumorigenesis when they were used in combination. AhR pathway may not be the key mechanism of this synergistic effect. Thus, it is necessary to further test the potential mechanism involved in cancer development.

关 键 词：DIOXIN Nitrosodiethylamine Cell transformation TUMORIGENESIS 

分 类 号：R730.2[医药卫生—肿瘤]