Chemically induced renal tubule tumors in the laboratory rat and mouse: review of the NCI/NTP database and categorization of renal carcinogens based on mechanistic information

Critical Reviews in Toxicology
Edward A Lock, Gordon C Hard

Abstract

The incidence of renal tubule carcinogenesis in male and female rats or mice with 69 chemicals from the 513 bioassays conducted to date by the NCI/NTP has been collated, the chemicals categorized, and the relationship between carcinogenesis and renal tubule hyperplasia and exacerbation of the spontaneous, age-related rodent disease chronic progressive nephropathy (CPN) examined. Where information on mechanism or mode of action exists, the chemicals have been categorized based on their ability to directly or indirectly interact with renal DNA, or on their activity via epigenetic pathways involving either direct or indirect cytotoxicity with regenerative hyperplasia, or exacerbation of CPN. Nine chemicals were identified as directly interacting with DNA, with six of these producing renal tubule tumors at high incidence in rats of both sexes, and in some cases also in mice. Ochratoxin A was the most potent compound in this group, producing a high tumor incidence at very low doses, often with metastasis. Three chemicals were discussed in the context of indirect DNA damage mediated by an oxidative free radical mechanism, one of these being from the NTP database. A third category included four chemicals that had the potential to caus...Continue Reading

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