{"corpus_id":27665431,"paper_sha":"6cdef11e92fb69d86167af599fafd8eda6810c86","doi":"10.1016/s0090-9556(25)06911-9","arxiv_id":null,"pmid":2898329,"pmcid":null,"mag_id":2305603634,"dblp_id":null,"acl_id":null,"title":"Regioselective and stereoselective metabolisms of pyrene and 1-bromopyrene by rat liver microsomes and effects of enzyme inducers.","year":1988,"publication_date":"1988-03-01","venue":"Drug Metabolism And Disposition","journal":{"name":"Drug metabolism and disposition: the biological fate of chemicals","pages":"\n          173-83\n        ","volume":"16 2"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article","Research Support, U.S. Gov't, P.H.S."],"s2_fields_of_study":["Medicine","Chemistry"],"reference_count":0,"citation_count":6,"influential_citation_count":0,"is_open_access":false,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Animals","mj":false,"ui":"D000818"},{"d":"Aroclors","mj":false,"qs":[{"q":"pharmacology","mj":false,"ui":"Q000494"}],"ui":"D001140"},{"d":"Chlorodiphenyl (54% Chlorine)","mj":false,"ui":"D020111"},{"d":"Chromatography, High Pressure Liquid","mj":false,"ui":"D002851"},{"d":"Enzyme Induction","mj":false,"qs":[{"q":"drug effects","mj":false,"ui":"Q000187"}],"ui":"D004790"},{"d":"Epoxy Compounds","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D004852"},{"d":"In Vitro Techniques","mj":false,"ui":"D066298"},{"d":"Male","mj":false,"ui":"D008297"},{"d":"Mass Spectrometry","mj":false,"ui":"D013058"},{"d":"Methylcholanthrene","mj":false,"qs":[{"q":"pharmacology","mj":false,"ui":"Q000494"}],"ui":"D008748"},{"d":"Microsomes, Liver","mj":false,"qs":[{"q":"drug effects","mj":false,"ui":"Q000187"},{"q":"enzymology","mj":false,"ui":"Q000201"},{"q":"metabolism","mj":true,"ui":"Q000378"}],"ui":"D008862"},{"d":"Phenobarbital","mj":false,"qs":[{"q":"pharmacology","mj":false,"ui":"Q000494"}],"ui":"D010634"},{"d":"Pyrenes","mj":false,"qs":[{"q":"metabolism","mj":true,"ui":"Q000378"}],"ui":"D011721"},{"d":"Rats","mj":false,"ui":"D051381"},{"d":"Rats, Inbred Strains","mj":false,"ui":"D011919"},{"d":"Spectrophotometry, Ultraviolet","mj":false,"ui":"D013056"},{"d":"Stereoisomerism","mj":false,"ui":"D013237"}],"chemicals":[{"n":"Aroclors","ui":"D001140","reg":"0"},{"n":"Epoxy Compounds","ui":"D004852","reg":"0"},{"n":"Pyrenes","ui":"D011721","reg":"0"},{"n":"Chlorodiphenyl (54% Chlorine)","ui":"D020111","reg":"11097-69-1"},{"n":"1-bromopyrene","ui":"C056303","reg":"1714-29-0"},{"n":"Methylcholanthrene","ui":"D008748","reg":"56-49-5"},{"n":"Phenobarbital","ui":"D010634","reg":"YQE403BP4D"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":null,"s2_open_access_landing_url":null,"s2_open_access_license":null,"s2_open_access_status":null,"pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"Due to the symmetrical property of pyrene (Py), trans-dihydrodiols formed at 4,5- and 9,10-positions are identical, as are the monohydroxylated products (phenols) formed at C1, C3, C6, and C8 positions. With a bromo substituent at C1 position of Py, 1-bromopyrene (1-BrPy) trans-4,5-dihydrodiol and 1-BrPy trans-9,10-dihydrodiol are distinctly different products, as are the phenolic products formed at C3, C6, and C8 positions. Products formed in the oxidative metabolism of 1-BrPy by rat liver microsomes were characterized by retention times on reversed-phase high performance liquid chromatography (HPLC), and by ultraviolet-visible absorption and mass spectral analyses. We have compared regioselective and stereoselective metabolisms at the K- and non-K-regions of Py and 1-BrPy by liver microsomes from untreated (control), phenobarbital (PB)-treated, 3-methylcholanthrene (MC)-treated, and polychlorinated biphenyls (PCB, Aroclor 1254)-treated rats. The effects of inducers on the relative amounts of non-K-region phenols formed in the metabolisms of Py and 1-BrPy by rat liver microsomes were: MC greater than PCB greater than PB greater than control. The relative order was PB greater than PCB greater than MC greater than control for the formation of both 1-BrPy trans-4,5-dihydrodiol and 1-BrPy trans-9,10-dihydrodiol in the metabolism of 1-BrPy. The ratios between metabolically formed 1-BrPy trans-4,5-dihydrodiol to Py trans-4,5-dihydrodiol, using 0.5 mg of microsomal protein per ml of incubation mixture, were between 0.4 and 0.6 in the presence of liver microsomes from untreated, PB-treated, and PCB-treated rats. However, the ratio was approximately 1.5 using liver microsomes from MC-treated rats. The ratios between the sum of 1-BrPy trans-9,10-dihydrodiol and 1-BrPy 9,10-epoxide to Py trans-9,10-dihydrodiol, and to 1-BrPy trans-4,5-dihydrodiol were in the range of 0.1 to 0.5 using four rat liver microsomal preparations. These data revealed the effects of a bromo substituent at C1 of Py on the regioselectivity of various rat liver microsomal enzymes toward the oxidative metabolism at various positions of 1-BrPy. The enantiomeric compositions of K-region dihydrodiols formed by four rat liver microsomal preparations were determined by chiral stationary phase HPLC and circular dichroism spectral analyses; the percentage of R,R-enantiomers were: Py trans-4,5-dihydrodiol, 78-79%; 1-BrPy trans-4,5-dihydrodiol, 74-77%; 1-BrPy trans-9,10-dihydrodiol, 86-97%.","claims":[{"public_id":"cl_ef410e3420611499fa8ea499824d6d09","status":"active","text":"3-methylcholanthrene-treated microsomes produced the highest relative amounts of non-K-region phenols, followed by polychlorinated biphenyl-treated, phenobarbital-treated, and untreated microsomes.","confidence":0.94,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_ef410e3420611499fa8ea499824d6d09"},{"public_id":"cl_a44f592f719f51738bf38783399a375f","status":"active","text":"A bromine substituent at C1 alters the regioselectivity of rat liver microsomal oxidation of pyrene, making the products from 1-bromopyrene distinguishable at the 4,5- and 9,10-positions.","confidence":0.96,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_a44f592f719f51738bf38783399a375f"},{"public_id":"cl_58a410a8af50a2ad23273e6a0e116fd5","status":"active","text":"Phenobarbital-treated microsomes produced 1-bromopyrene trans-4,5-dihydrodiol and 1-bromopyrene trans-9,10-dihydrodiol more strongly than 3-methylcholanthrene-treated microsomes, with the order phenobarbital greater than polychlorinated biphenyls greater than 3-methylcholanthrene greater than control.","confidence":0.92,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_58a410a8af50a2ad23273e6a0e116fd5"},{"public_id":"cl_ee9d835f1b8c0d8d6820b06206b29662","status":"active","text":"The proportion of R,R-enantiomers was 78-79% for pyrene trans-4,5-dihydrodiol, 74-77% for 1-bromopyrene trans-4,5-dihydrodiol, and 86-97% for 1-bromopyrene trans-9,10-dihydrodiol.","confidence":0.98,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_ee9d835f1b8c0d8d6820b06206b29662"}],"concepts":[{"public_id":"co_2b7763c45a0dc32f60f337b7094e6292","status":"active","name":"pyrene trans-4,5-dihydrodiol","description":"A trans-dihydrodiol metabolite of pyrene formed at the 4,5-position.","types":["metabolite"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_2b7763c45a0dc32f60f337b7094e6292"},{"public_id":"co_30226d9ed13f922877ef5ae1bce07c0c","status":"active","name":"HPLC","description":"A chromatographic method used to separate and identify oxidative metabolites by retention time.","types":["analytical method"],"aliases":["high performance liquid chromatography"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_30226d9ed13f922877ef5ae1bce07c0c"},{"public_id":"co_3831343a8c4f3bcd9c1f2f0101da7ab2","status":"active","name":"pyrene","description":"A symmetric polycyclic aromatic hydrocarbon used here as the parent substrate for microsomal oxidation.","types":["compound"],"aliases":["Py"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_3831343a8c4f3bcd9c1f2f0101da7ab2"},{"public_id":"co_3fb1232d8437a2290f1c3cdb916b8dbc","status":"active","name":"1-bromopyrene trans-9,10-dihydrodiol","description":"A trans-dihydrodiol metabolite of 1-bromopyrene formed at the 9,10-position.","types":["metabolite"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_3fb1232d8437a2290f1c3cdb916b8dbc"},{"public_id":"co_49e0b8727e6f91400f521fd8d9d403ad","status":"active","name":"non-K-region phenols","description":"Monohydroxylated oxidation products formed at the non-K-region positions of pyrene derivatives.","types":["metabolite class"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_49e0b8727e6f91400f521fd8d9d403ad"},{"public_id":"co_4a52c228f677998ce23c033005e3c94a","status":"active","name":"polychlorinated biphenyls","description":"A mixture of chlorinated biphenyl compounds used here as an enzyme inducer.","types":["enzyme inducer"],"aliases":["PCB","Aroclor 1254"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_4a52c228f677998ce23c033005e3c94a"},{"public_id":"co_5d9b3253b1e5388a6817cd763b90e38b","status":"active","name":"3-methylcholanthrene","description":"A rat treatment used as an enzyme inducer before microsome preparation.","types":["enzyme inducer"],"aliases":["MC"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_5d9b3253b1e5388a6817cd763b90e38b"},{"public_id":"co_8240629baa434609ccae644c621ee05b","status":"active","name":"rat liver microsomes","description":"Microsomal liver preparations from rats used to catalyze oxidative metabolism of the compounds.","types":["biological preparation"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_8240629baa434609ccae644c621ee05b"},{"public_id":"co_ae6e3219f3414f031e91099a47527959","status":"active","name":"1-bromopyrene","description":"A brominated pyrene derivative with a substituent at the C1 position.","types":["compound"],"aliases":["1-BrPy"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_ae6e3219f3414f031e91099a47527959"},{"public_id":"co_b0a6976d0d3892950e6e0493ce6e68bf","status":"active","name":"R,R-enantiomers","description":"The R,R stereochemical form among the chiral dihydrodiol metabolites measured in this study.","types":["stereoisomer"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_b0a6976d0d3892950e6e0493ce6e68bf"},{"public_id":"co_e48841103c86c6e9f5af375a08b627d2","status":"active","name":"regioselectivity","description":"Selectivity for oxidation at particular positions on the aromatic ring system.","types":["chemical property"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_e48841103c86c6e9f5af375a08b627d2"},{"public_id":"co_e656df1d01df6935a81ff6afae733a3b","status":"active","name":"1-bromopyrene trans-4,5-dihydrodiol","description":"A trans-dihydrodiol metabolite of 1-bromopyrene formed at the 4,5-position.","types":["metabolite"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_e656df1d01df6935a81ff6afae733a3b"},{"public_id":"co_fd12ee74555e57b196497b4af4ef3448","status":"active","name":"phenobarbital","description":"A rat treatment used as an enzyme inducer before microsome preparation.","types":["enzyme inducer"],"aliases":["PB"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_fd12ee74555e57b196497b4af4ef3448"},{"public_id":"co_fdfbb29f737410625c35ec83d622d0c0","status":"active","name":"stereoselectivity","description":"Preference for forming one stereochemical outcome or enantiomeric composition over another.","types":["chemical property"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_fdfbb29f737410625c35ec83d622d0c0"}],"external_ids":{"DOI":"10.1016/s0090-9556(25)06911-9","ArXiv":null,"PubMed":2898329,"PubMedCentral":null,"MAG":2305603634,"DBLP":null,"ACL":null},"open_access":{"is_open_access":false,"pdf_url":null,"landing_url":"https://sah.borca.ai/papers/27665431","source":null,"pdf_url_source":null,"license":null,"reason":"pdf_url_not_indexed"},"reference_availability":{"status":"unknown","references_indexed":false,"full_text_available":false,"full_text_source":null,"count_basis":"semantic_scholar_metadata","extraction_status":"not_applicable","reason":null},"source":{"provider":"episteme2","base_corpus":"semantic_scholar_dump","freshness_mode":"unknown","basis":["semantic_scholar_metadata","postgres_metadata"],"limits":["paper metadata is based on indexed upstream scholarly datasets","claims and concepts are available only for extracted papers","absence of claims or concepts means no extracted graph data is available in this response"],"status":"available","degraded":false,"degraded_reasons":[],"diagnostics":{"status":"available","degraded":false,"degraded_reasons":[],"metadata_status":"available","graph_status":"available","abstract_status":"available"},"source_flags":5},"paper_id":632911,"paper_uid":"1c0a3dc4-1169-4362-b316-09b54b124131","canonical_identity":{"paper_id":632911,"paper_uid":"1c0a3dc4-1169-4362-b316-09b54b124131","identity_status":"available","lookup_basis":"semantic_scholar_external_id","compatibility_path":"corpus_id"},"url":"https://sah.borca.ai/papers/27665431"}