We found that the HL cytosols used were from individuals with different SULT1A1 genotypes, as determined by PCR amplification of the region of the SULT1A gene flanking the polymorphic base pair.
We observed substrate inhibition in HL cytosol and with SULT1A1 and SULT1E1, but not with SULTIA3 or SULT1B1.
0 [micro]M 3-OH-BaP, a concentration that produced substrate inhibition in liver cytosol and with both SULT1A1 variants, the OH-PCBs were considerably less potent inhibitors in cytosol and even more so with the expressed SULT1A1*1 and SULTIA12 enzymes (Table 3 and data not shown).
We could not discern any other clear relationship of inhibitory potency with structural features or with physicochemical properties of the OH-PCBs in this relatively small series of compounds, with cytosol or the two expressed SULT1A1 enzymes.
SULT1B1, the thyroid hormone sulfotransferase, catalyzed the sulfonation of 3-OH-BaP; however, OH-PCBs that were potent inhibitors of SULT1A1 were only weak inhibitors of the SULT1Bl-catalyzed reaction.
Although these were generally less potent as inhibitors of SULT1A1 than the type B OH-PCBs, it is possible that the concentrations of these OH-PCBs may reach inhibitory levels in tissues of highly exposed people or animals.
We found that several OH-PCBs, especially those with a 3-chloro-4-hydroxy substitution pattern in the phenolic ring, inhibited the sulfonation of 3-OH-BaP in cytosol and with SULT1A1 at submicromolar concentrations.