Sulfonation of environmental chemicals and their metabolites in the polar bear (Ursus maritimus).
Although its habitat comprises mostly remote regions of the Arctic, the polar bear is subject to bioaccumulation of persistent environmental pollutants. Along with their phase I metabolites, they are potential substrates for detoxification via sulfonation and glucuronidation. The capability of polar bear liver to sulfonate a structurally diverse group of environmental chemicals, that is, 3-hydroxybenzo[a]pyrene (3-OH-B[a]P), triclosan, 4'-hydroxy-3,3',4,5'-tetrachlorobiphenyl (4'OH-PCB79), 4'-hydroxy-2,3,3',4,5,5'-hexachlorobiphenyl (4'-OH-PCB159), 4'-hydroxy-2,3,3',5,5',6-hexachlorobiphenyl (4'-OH-PCB165), the methoxychlor metabolite 2-(4-methoxyphenyl)-2-(4-hydroxyphenyl)-1,1,1-trichloroethane (OHMXC), tris(4-chlorophenyl)-methanol (TCPM), and pentachlorophenol (PCP) was investigated. The glucuronidation of 3-OH-B[a]P was also studied. Enzyme activity was assayed by incubation of liver cytosol or microsomes derived from three adult male polar bears with 3'-phosphoadenosine-5'-phosphosulfate or uridine 5'-diphosphoglucuronic acid and substrate, followed by fluorometric or radiochemical thin-layer chromatographic analysis. The efficiency of sulfonation decreased in the order 3-OH-B[a]P >>> triclosan >> 4'-OH-PCB79 > OHMXC > 4'-OH-PCB165 > TCPM > 4'-OH-PCB159 > PCP, all of which produced detectable sulfate conjugates. The 3-OH-B[a]P substrate was readily sulfonated and glucuronidated (apparent K(m) 0.41, 1.4 microM, and apparent V(max) 0.50, 3.00 nmol/min/mg, respectively). UDP-glucuronic acid kinetics suggested the presence of multiple enzymes glucuronidating 3-OH-B[a]P. Substrate inhibition was observed for the sulfonation of 3-OH-B[a]P and 4'OH-PCB79 (K(i) 1.0 and 217 microM, respectively). Triclosan was the most rapidly sulfated (apparent V(max) 1008 pmol/min/mg) of the substrates tested. Since sulfonation of an acyclic tertiary alcoholic group, as in TCPM, has not previously been reported, we also examined TCPM conjugation in humans and catfish, both of which formed TCPM-sulfate. The hexachlorinated polychlorinated biphenylols, TCPM, and PCP were poor substrates for sulfonation, suggesting that this may be one reason why these substances and structurally similar xenobiotics persist in polar bears.
Sacco
James C
JC
Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA.
James
Margaret O
MO
D000818:Animals; D002478:Cells, Cultured; D003600:Cytosol / Q000201:enzymology / Q000378:metabolism; D004785:Environmental Pollutants / Q000378:metabolism*; D014453:Glucuronosyltransferase / Q000378:metabolism*; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism; D015238:Sulfotransferases / Q000378:metabolism*; D001503:Ursidae / Q000378:metabolism*; D015262:Xenobiotics / Q000378:metabolism*
D004785:Environmental Pollutants; D015262:Xenobiotics; D014453:Glucuronosyltransferase; D015238:Sulfotransferases