{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T20:41:29Z","timestamp":1758400889192},"reference-count":29,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2006,7,19]],"date-time":"2006-07-19T00:00:00Z","timestamp":1153267200000},"content-version":"vor","delay-in-days":5313,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[1992,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Increased expression of multidrug\u2010resistance (<jats:italic>mdr<\/jats:italic>) gene transcripts and of the encoded protein, P\u2010glycoprotein, is found in many types of tumors. The biological significance of <jats:italic>mdr<\/jats:italic> overexpression during the stepwise process of neoplastic development, however, is not well understood. To assess the possible significance of <jats:italic>mdr<\/jats:italic> overexpression in carcinogenesis, we examined the cellular distributions of both <jats:italic>mdr<\/jats:italic> gene transcripts and P\u2010glycoprotein during hepatocarcinogenesis induced in rats by the Solt\u2010Farber protocol and then compared them to the distributions of the placental form of glutathione S\u2010transferase (GST\u2010P), a known marker of preneoplastic and neoplastic lesions in the liver. In situ hybridization and immunohistochemical techniques were employed. Neither <jats:italic>mdr<\/jats:italic> transcripts nor P\u2010glycoprotein was expressed in oval cells that appeared early in the carcinogenic process. GST\u2010P was strongly expressed in the early focal lesions, whereas the levels of <jats:italic>mdr<\/jats:italic> transcripts and P\u2010glycoprotein expressed were low and heterogeneous. Expression of <jats:italic>mdr<\/jats:italic> transcripts and P\u2010glycoprotein was increased and became more uniform in hyperplastic nodules and carcinomas, although considerable heterogeneity of expression was still found, particularly at the nodular stage. These data suggest that increased expression of <jats:italic>mdr<\/jats:italic> is associated with later stages of neoplastic development in the liver. Furthermore, that no chemical treatment of the animals was employed when the expression of <jats:italic>mdr<\/jats:italic> was increasing in the preneoplastic and neoplastic lesions suggests that the enhanced <jats:italic>mdr<\/jats:italic> expression is intrinsic to the carcinogenic process. \u00a9 1992 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/mc.2940060304","type":"journal-article","created":{"date-parts":[[2007,2,21]],"date-time":"2007-02-21T20:44:39Z","timestamp":1172090679000},"page":"190-198","source":"Crossref","is-referenced-by-count":18,"title":["Cellular pattern of multidrug\u2010resistance gene expression during chemical hepatocarcinogenesis in the rat"],"prefix":"10.1002","volume":"6","author":[{"given":"Harushige","family":"Nakatsukasa","sequence":"first","affiliation":[]},{"given":"Ritva P.","family":"Evarts","sequence":"additional","affiliation":[]},{"given":"Richard K.","family":"Burt","sequence":"additional","affiliation":[]},{"given":"Peter","family":"Nagy","sequence":"additional","affiliation":[]},{"given":"Snorri S.","family":"Thorgeirsson","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2006,7,19]]},"reference":[{"key":"e_1_2_1_2_2","first-page":"3879","article-title":"The resistance of putative premalignant liver cell populations, hyperplastic nodules, to the acute cytotoxic effects of some hepatocarcinogens","volume":"36","author":"Farber E","year":"1976","journal-title":"Cancer Res"},{"key":"e_1_2_1_3_2","first-page":"5577","article-title":"Pleiotropic drug resistance in hepatocytes induced by carcinogens administered to rats","volume":"47","author":"Carr BI","year":"1987","journal-title":"Cancer 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