QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: dmd.105.004648v1 33/9/1341    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sacco, J. C. Articles by James, M. O. Search for Related Content PubMed PubMed Citation Articles by Sacco, J. C. Articles by James, M. O.

SULFONATION OF ENVIRONMENTAL CHEMICALS AND THEIR METABOLITES IN THE POLAR BEAR (Ursus maritimus)

Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville Florida

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 µM, 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 µM, 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.

This article has been cited by other articles:

				D Pugazhendhi, K A Watson, S Mills, N Botting, G S Pope, and P D Darbre Effect of sulphation on the oestrogen agonist activity of the phytoestrogens genistein and daidzein in MCF-7 human breast cancer cells J. Endocrinol., June 1, 2008; 197(3): 503 - 515. [Abstract] [Full Text] [PDF]

				J. C. Sacco, H.-J. Lehmler, L. W. Robertson, W. Li, and M. O. James Glucuronidation of Polychlorinated Biphenylols and UDP-Glucuronic Acid Concentrations in Channel Catfish Liver and Intestine Drug Metab. Dispos., April 1, 2008; 36(4): 623 - 630. [Abstract] [Full Text] [PDF]