Transcriptional effects of Organochlorine o,p′-DDT and its Metabolite p,p′-DDE in Transfected MDA-MB 231 and MCF-7 Breast Cancer Cell Lines

Background: The organochlorine DDT has estrogenic activity but the mechanism underlying the estrogenic activity of this pesticide remains unclear. In the present investigation, we studied the transcriptional effects of a synthetic organochlorine pesticide o,p′-DDT [1.1.1.-trichloro-2-(o-chlorophenyl)-2-p-chloriphenyl ethane] and its metabolite p,p -DDE (2-2-bis(4/chlorophenyl)-1-1-dichloroethyl) on the bovine oxytocin and the thymidine kinase-ERE promoter by estrogen receptor α in MDA-MB 231 and MCF-7 breast cancer cell lines. Materials and Methods: Cells were seeded for transfection into 12- well plates at a density of 100000 cells per well and were transfected with a total of 3 μg of plasmid DNA using calcium phosphate coprecipitation. o,p′-DDT and p,p -DDE were used for stimulation of transfected MDA-MB 231 and MCF-7 breast cancer cell lines. Results: o,p′-DDT showed no agonistic activity in MDA-MB 231 cells transfected with the oxytocin promoter construct (OTwt) or the thymidine kinase-ERE promoter construct (TK ERE) and estrogen receptor α. While, we found o,p′-DDT with an agonistic effect on both the oxytocin and the thymidine kinase-ERE promoter in MCF-7 leading to a more than two-fold stimulation of transcription at 10-5 M. Moreover, there was no agonistic effect with p,p -DDE on transfected MCF-7 cells and MDA-MB 231 cell lines. Conclusion: In conclusion, o,p′-DDT was not found to have any estrogenic activity in a classical mechanism in transfected MDA-MB 231 breast cancer cells while it showed estrogenic activity in a classical mechanism in transfected MCF-7 human breast cancer cell line.