{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,5,31]],"date-time":"2024-05-31T06:30:08Z","timestamp":1717137008647},"reference-count":62,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2001,5,22]],"date-time":"2001-05-22T00:00:00Z","timestamp":990489600000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2001,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Although hydroquinone (HQ) is a rodent carcinogen, because of its lack of mutagenicity in standard bacterial mutagenicity assays it is generally considered a nongenotoxic carcinogen. 2,3,5\u2010<jats:italic>Tris<\/jats:italic>\u2010(glutathion\u2010<jats:italic>S<\/jats:italic>\u2010yl)HQ (TGHQ) is a potent nephrotoxic metabolite of HQ that may play an important role in HQ\u2010mediated nephrocarcinogenicity. TGHQ mediates cell injury by generating reactive oxygen species and covalently binding to tissue macromolecules. We determined the ability of HQ and TGHQ to induce cell transformation in primary renal epithelial cells derived from the Eker rat. Eker rats possess a germline inactivation of one allele of the tuberous sclerosis\u20102 (<jats:italic>Tsc\u20102<\/jats:italic>) tumor suppressor gene that predisposes the animals to renal cell carcinoma. Treatment of primary Eker rat renal epithelial cells with HQ (25 and 50 \u03bcM) or TGHQ (100 and 300 \u03bcM) induced 2\u2010 to 4\u2010fold and 6\u2010 to 20\u2010fold increases in cell transformation, respectively. Subsequently, three cell lines (The QT\u2010RRE 1, 2, and 3) were established from TGHQ\u2010induced transformed colonies. The QT\u2010RRE cell lines exhibited a broad range of numerical cytogenetic alterations, loss of heterozygosity at the <jats:italic>Tsc\u20102<\/jats:italic> gene locus, and loss of expression of tuberin, the protein encoded by the <jats:italic>Tsc\u20102<\/jats:italic> gene. Only heterozygous (<jats:italic>Tsc<\/jats:italic>\u2010<jats:italic>2<\/jats:italic><jats:sup>EK\/+<\/jats:sup>) kidney epithelial cells were susceptible to transformation by HQ and TGHQ, as wild\u2010type cells (<jats:italic>Tsc\u20102<\/jats:italic><jats:sup>+\/+<\/jats:sup>) showed no increase in transformation frequency over background levels following chemical exposure. These data indicate that TGHQ and HQ are capable of directly transforming rat renal epithelial cells and that the <jats:italic>Tsc\u2010<\/jats:italic>2 tumor suppressor gene is an important target of TGHQ\u2010mediated renal epithelial cell transformation. \u00a9 2001 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/mc.1037","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T20:35:44Z","timestamp":1030307744000},"page":"37-45","source":"Crossref","is-referenced-by-count":11,"title":["Transformation of kidney epithelial cells by a quinol thioether via inactivation of the tuberous sclerosis\u20102 tumor suppressor gene"],"prefix":"10.1002","volume":"31","author":[{"given":"Hae\u2010Seong","family":"Yoon","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Terrence J.","family":"Monks","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheryl L.","family":"Walker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Serrine S.","family":"Lau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2001,5,22]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8052857"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0278-6915(92)90075-V"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.1991.tb01783.x"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.97105s4875"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1080\/10408449991349221"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.2307\/3429556"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1080\/009841096161915"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19950515)75:10<2552::AID-CNCR2820751023>3.0.CO;2-1"},{"key":"e_1_2_7_10_2","first-page":"93","article-title":"Epidemiology of renal\u2010cell carcinoma","volume":"10","author":"Tavani A","year":"1997","journal-title":"J Nephrol"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1080\/15287398509530777"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.93100293"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0300-483X(80)90055-4"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1218(85)90007-2"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-1218(96)90118-4"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1218(81)90072-0"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0027-5107(96)00196-0"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3835(92)90088-D"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1998.492"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.3109\/00498259209051867"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-4274(93)90052-Y"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004320050260"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/0041-008X(90)90100-9"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/18.12.2393"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1021\/tx000161g"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1021\/tx990160s"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4757-9480-9_35"},{"key":"e_1_2_7_28_2","first-page":"3641","article-title":"Quinol\u2010glutathione conjugate\u2010induced mutation spectra in the supF gene replicated in human AD293 cells and bacterial MBL50 cells","volume":"59","author":"Jeong JK","year":"1999","journal-title":"Cancer Res"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.1021\/tx9801357"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/189858b0"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1553556"},{"key":"e_1_2_7_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0195-70"},{"key":"e_1_2_7_33_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1994.2324"},{"key":"e_1_2_7_34_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.24.11413"},{"key":"e_1_2_7_35_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.17.8038"},{"key":"e_1_2_7_36_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.1993.tb02808.x"},{"key":"e_1_2_7_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(17)37087-8"},{"key":"e_1_2_7_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3835(94)90307-7"},{"key":"e_1_2_7_39_2","first-page":"1556","article-title":"Rodent model of reproductive tract leiomyomata. 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