The Effects of Legacy and Emerging Persistent Organic Pollutants in Endocrine Signalling Pathways in Mammalian Cancer Cell Lines

Despite its ban, DDT and DDE are still persistent in the environment. TBECH is a brominated flame retardant that has been detected in the biota. Here, we determined whether p,p’-DDT, p,p’-DDE and TBECH can negatively impact androgen receptor (AR)-regulated expression of prostate-specific antigen (PSA), prostate-specific membrane antigen (PSMA) and AR in human LNCaP cells. Real-time PCR, Western-blotting and COBAS PSA detection system were used to measure mRNA and protein levels. Chromatin-immunoprecipitation assay was used to determine AR-PSA promoter interaction. My results showed that p,p’-DDT and p,p’-DDE repressed R1881-inducible PSA mRNA and protein levels by blocking recruitment of AR to the PSA promoter. p,p’-DDT and p,p’-DDE can also significantly repress AR protein levels and relieve R1881-inducible PSMA repression. TBECH was found to repress R1881-inducible PSA protein levels. I conclude that men who have been exposed to either DDT or DDE may produce a false-negative PSA test when screening for prostate cancer.