Effects of pentachlorophenol and hydroxylated polychlorinated biphenyls onthyroid hormone conjugation in a rat and a human hepatoma cell line

It was previously demonstrated in our laboratory that hydroxylated metaboli tes of poly chlorinated biphenyls (PCB-OHs) inhibit the sulfation of iodoth yronines in rat liver cytosol. In this study, the inhibition of 3,3'-diiodo thyronine (T2?) sulfation by pentachlorophenol (PCP) and PCB-OHs was invest igated in hepatoma cell lines in relation to the cellular uptake of these c ompounds. providing a more appropriate model of the bt vivo situation. The human HepG2 hepatoma cell line was shown to conjugate T2 almost exclusively by sulfation, glucuronidation bring negligible. The rat FaO hepatoma cell line, on the other hand, produced 37% T2 sulfate and 63% T2 glucuronide. It was demonstrated that PCP inhibited T2? sulfation in both cell lines, alth ough it was 10(3) times less potent in cells than in rat liver cytosol. Rem arkably, 10 mu M PCP inhibited the sulfation and glucuronidation of T2 by F aO cells to the same extent. Micromolar concentrations of 4-hydroxy-3,3',4' ,5-tetrachlorobiphenyl or 4-hydroxy-2',3,3'.4'.5-pentachlorobiphenyl hardly affected T2 conjugation in FaO cells, but both PCB-OHs reduced T2? sulfate formation in HepG2? cells. Inhibition of T2 sulfation was stronger using m edium without foetal calf serum (FCS) than medium with 5% FCS. This was due to a lower uptake of inhibitor by the cells in the presence of serum, as d emonstrated using radiolabelled PCP. In conclusion, this study confirms the inhibition of T2 sulfation by PCP and PCB-OHs previously observed in rat l iver cytosol in a rat and a human hepatoma cell line. Thus, it seems reason able to assume that iodothyronine sulfation is also inhibited by PCB metabo lites and PCP ill vivo. (C) 1999 Elsevier, Science Ltd. All rights reserved .