PMID: 11901093Mar 20, 2002Paper

Glucuronidation: an important mechanism for detoxification of benzo[a]pyrene metabolites in aerodigestive tract tissues

Drug Metabolism and Disposition : the Biological Fate of Chemicals
Zhong ZhengPhilip Lazarus

Abstract

UDP-glucuronosyltransferases (UGTs) have been implicated as important detoxifying enzymes for several major tobacco carcinogens. Because the aerodigestive tract is a primary target for exposure to tobacco smoke carcinogens, the major goal of the present study was to determine whether aerodigestive tract tissues exhibit glucuronidating activity against metabolites of benzo[a]pyrene (BaP) and to explore the pattern of expression of UGT genes in a series of aerodigestive tract tissue specimens. Glucuronidation of the phenolic BaP metabolites 3-, 7-, and 9-hydroxy-BaP was observed in all upper aerodigestive tract tissue microsome specimens tested, as determined by high-pressure liquid chromatography analysis. Glucuronidating activity toward the procarcinogenic BaP metabolite trans-BaP-7,8-dihydrodiol(+/-) was also detected in aerodigestive tract tissues. By semiquantitative duplex reverse transcription-polymerase chain reaction analysis, UGT1A7 and UGT1A10 were shown to be well expressed in all aerodigestive tract tissues examined, including tongue, tonsil, floor of mouth, larynx, and esophagus. UGT1A8 and UGT1A6 were expressed primarily in larynx; no expression was observed for UGTs 1A1, 1A3, 1A4, 1A5, 1A9. Of the family 2B UGTs, ...Continue Reading

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