title: Synergistic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin and N-nitrosodiethylamine on cell malignant transformation.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Key Laboratory of Food Safety Risk Assessment, Ministry of Health, China National Center for Food Safety Risk Assessment, Beijing 100022, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Rui
authors.initials: R
authors.lastname: Zhao
authors.forename: Shu Qing
authors.initials: SQ
authors.lastname: Ye
authors.forename: Ling
authors.initials: L
authors.lastname: Zhou
authors.forename: Yong Ning
authors.initials: YN
authors.lastname: Wu
authors.forename: Yi
authors.initials: Y
authors.lastname: Zeng
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D002273:Carcinogens / Q000633:toxicity*; D002471:Cell Transformation, Neoplastic; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D017931:DNA Primers; D004052:Diethylnitrosamine / Q000633:toxicity*; D004357:Drug Synergism; D051379:Mice; D008807:Mice, Inbred BALB C; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D002273:Carcinogens; D017931:DNA Primers; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D004052:Diethylnitrosamine; D003577:Cytochrome P-450 Enzyme System
keywords: Cell transformation; Dioxin; Nitrosodiethylamine; Tumorigenesis