Effects of pentachlorophenol and hydroxylated polychlorinated biphenyls on thyroid hormone conjugation in a rat and a human hepatoma cell line.
It was previously demonstrated in our laboratory that hydroxylated metabolites of polychlorinated biphenyls (PCB-OHs) inhibit the sulfation of iodothyronines in rat liver cytosol. In this study, the inhibition of 3,3'-diiodothyronine (T2) sulfation by pentachlorophenol (PCP) and PCB-OHs was investigated in hepatoma cell lines in relation to the cellular uptake of these compounds, providing a more appropriate model of the in vivo situation. The human HepG2 hepatoma cell line was shown to conjugate T2 almost exclusively by sulfation, glucuronidation being 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, although it was 10(3) times less potent in cells than in rat liver cytosol. Remarkably, 10 mumPCP inhibited the sulfation and glucuronidation of T2 by FaO 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 medium 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 demonstrated using radiolabelled PCP. In conclusion, this study confirms the inhibition of T2 sulfation by PCP and PCB-OHs previously observed in rat liver cytosol in a rat and a human hepatoma cell line. Thus, it seems reasonable to assume that iodothyronine sulfation is also inhibited by PCB metabolites and PCP in vivo.
Schuur
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AG
Toxicology Group, Department of Food Technology and Nutritional Sciences, Agricultural University Wageningen, PO Box 8000, 6700 EA Wageningen, The Netherlands.
Bergman
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A
Brouwer
A
A
Visser
T J
TJ