Effects of single non-ortho, mono-ortho, and di-ortho chlorinated biphenyls on cell functions and proliferation of the human prostatic carcinoma cell line, LNCaP.
This study investigated the effects of the non-ortho 3,3',4,4',5-pentachlorobiphenyl (PCB 126) and 3,3',4,4'-tetrachlorobiphenyl (PCB 77), the mono-ortho 2,3',4,4',5-pentachlorobiphenyl (PCB 118), and the di-ortho substituted 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153) on the human prostatic carcinoma cell line LNCaP. Activities of 5alpha-reductase and ethoxyresorufin-O-deethylase (EROD) secretion of testosterone-regulated prostatic specific antigen (PSA) and cell proliferation served as specific and general cell markers. The two non-ortho (dioxin-like) PCBs, PCB 126 and PCB 77, showed anti-androgenic properties. Both PCBs reduced androgen-depending PSA secretion and cell proliferation, and inhibited the DHT-producing enzyme 5alpha-reductase in a concentration-dependent manner. In contrast, the ortho-substituted PCBs, PCB 118 and PCB 153, had no effect on 5alpha-reductase. However, they had a biphasic effect on LNCaP cell proliferation. PCB 153 and, to some extent, PCB 118 induced cell proliferation and PSA secretion at low concentrations, whereas, these parameters were reduced at high concentrations. Since EROD induction and inhibition of 5alpha-reductase activity was not observed, these findings suggest an AhR and AR independent mechanism and post-transcriptional target sites should be considered. The effects of PCB 126 on cell proliferation, PSA secretion, and 5alpha-reductase activity may be partly a result of AhR-dependent inhibition. In conclusion, the endocrine activity of PCBs via direct steroid hormone receptor-mediated and Ah receptor-mediated pathways are well known. However, the modulation of post-transcriptional targets may account for some of the endocrine disrupting properties of single PCB congeners.
Endo
Fumiyasu
F
Center of Dermatology and Andrology, Justus Liebig University of Giessen, Gaffky Str. 14, 35385, Giessen, Germany.
Monsees
Thomas K
TK
Akaza
Hideyuki
H
Schill
Wolf Bernhard
WB
Pflieger-Bruss
Sybille
S
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism; D001713:Biphenyl Compounds / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D004785:Environmental Pollutants / Q000633:toxicity*; D006801:Humans; D007700:Kinetics; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000473:pathology*; D011944:Receptors, Androgen / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D013739:Testosterone / Q000502:physiology; D014407:Tumor Cells, Cultured
D001713:Biphenyl Compounds; D004785:Environmental Pollutants; D009363:Neoplasm Proteins; D011944:Receptors, Androgen; D018336:Receptors, Aryl Hydrocarbon; D013739:Testosterone; D011078:Polychlorinated Biphenyls; D019363:Cytochrome P-450 CYP1A1; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; D017430:Prostate-Specific Antigen