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However, almost all of our knowledge concerning mechanisms of renal carcinogenesis in the rodent pertains to the adenomas and carcinomas originating from renal tubule epithelium. Currently, nine mechanistic pathways can be identified in either the rat or mouse following chemical exposure. These include direct DNA reactivity, indirect DNA reactivity through free radical formation, multiphase bioactivation involving glutathione conjugation, mitotic disruption, sustained cell proliferation from direct cytotoxicity, sustained cell proliferation by disruption of a physiologic process (alpha 2u-globulin nephropathy), exaggerated pharmacologic response, species-dominant metabolic pathway, and chemical exacerbation of chronic progressive nephropathy. Spontaneous occurrence of RTTs in the rat will be included since one example is a confounder for interpreting kidney tumor results in chemical carcinogenicity studies in rats.<\/jats:p>","DOI":"10.1177\/0192623318797071","type":"journal-article","created":{"date-parts":[[2018,10,1]],"date-time":"2018-10-01T07:55:52Z","timestamp":1538380552000},"page":"956-969","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":8,"title":["Mechanisms of Rodent Renal Carcinogenesis Revisited"],"prefix":"10.1177","volume":"46","author":[{"given":"Gordon C.","family":"Hard","sequence":"first","affiliation":[{"name":"Tairua, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2018,10,1]]},"reference":[{"key":"bibr1-0192623318797071","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgp049"},{"key":"bibr2-0192623318797071","doi-asserted-by":"publisher","DOI":"10.1177\/030098588101800413"},{"key":"bibr3-0192623318797071","doi-asserted-by":"publisher","DOI":"10.3109\/10408448809037470"},{"key":"bibr4-0192623318797071","doi-asserted-by":"publisher","DOI":"10.1016\/0015-6264(81)90516-2"},{"key":"bibr5-0192623318797071","unstructured":"Baetcke K. 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