Transcriptional effects of Organochlorine o,p′-DDT and its Metabolite p,p′-DDE in Transfected MDA-MB ۲۳۱ and MCF-۷ 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 here, we studied the transcriptional effects of a synthetic organochlorine pesticide o,p’-DDT [۱.۱.۱.-trichloro-۲-(o-chlorophenyl)-۲-p-chloriphenyl ethane] and its metabolite p,p'-DDE (۲-۲-bis(۴/chlorophenyl)-۱-۱-dichloroethyl) on the bovine oxytocin and the thymidine kinase-ERE promoter by estrogen receptor &alpha in MDA-MB ۲۳۱ and MCF-۷ breast cancer cell line. Materials and Methods: Cells were seeded for transfections into ۱۲- well plates at a density of ۱۰۰۰۰۰ cells per well and were transfected with a total of ۳ &mug of plasmid DNA using calcium phosphate coprecipitation. o,p’-DDT and p,p'-DDE were used for stimulation of transfected MDA-MB ۲۳۱ and MCF-۷ breast cancer cell lines. Results: The results showed o,p’-DDT has no agonistic activity in MDA-MB ۲۳۱ cells transfected with the oxytocin promoter construct (OTwt) or the thymidine kinase-ERE promoter construct (TK ERE) and estrogen receptor &alpha. While, The results obviously show that o,p’-DDT has an agonistic effect on both the oxytocin and the thymidine kinase-ERE promoter in MCF-۷ leading to a more than two-fold stimulation of transcription at ۱۰-۵ M. In addition, there is no agonistic effect with p,p'-DDE on transfected MCF-۷ cells and MDA-MB ۲۳۱ cell line. Conclusion: In conclusion, our results revealed that o,p’-DDT has not estrogenic activity in a classical mechanism in transfected MDA-MB ۲۳۱ breast cancer cells while has estrogenic activity in a classical mechanism in transfected MCF-۷ human breast cancer cell line.

Keywords:

Organochlorinated pesticides , o , p’-DDT , MCF-۷ cell line , thymidine kinase-ERE promoter.