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Spontaneous Occurrence of a Distinctive Renal Tubule Tumor Phenotype in Rat Carcinogenicity Studies Conducted by the National Toxicology Program

¹ Private Consultant, Tairua, New Zealand
² Experimental Pathology Laboratories Inc, Research Triangle Park, North Carolina, USA
³ National Institutes of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina, USA
⁴ Constella Health Sciences, Durham, North Carolina, USA

Correspondence: Address correspondence to: G. C. Hard, PO Box 86, Tairva 3544, New Zealand; e-mail:gordonhard{at}msn.com.

The Toxicology Data Management System (TDMS) of the National Toxicology Program, National Institutes of Environmental Health Sciences, National Institutes of Health, was surveyed for occurrence and distribution of a distinctive renal tubule tumor type in rats. The hallmark features of this tumor included eosinophilic/amphophilic staining, large finely granular cells, and numerous vacuoles and/or minilumens. It is referred to here as the amphophilic-vacuolar (AV) variant of renal tubule tumor. Of 154 studies in which renal tubule tumors had been recorded in the standard single sections of kidney in the TDMS, there were collectively 1012 rats with renal adenomas, carcinomas, or adenocarcinomas, and of these, 100 displayed the distinctive AV morphology, representing 74 studies involving mostly the F344 rat, but also the Sprague-Dawley and Wistar strains. The AV tumors (mainly adenomas but also some carcinomas) occurred usually as solitary lesions in the affected animals. However, they were multiple and bilateral in a few cases. They were equally distributed between the sexes, did not metastasize (at least to the lung), and were not associated with chronic progressive nephropathy. The distribution of this renal tumor type was random across studies and dose groups, underscoring the likelihood that it was of spontaneous origin and not chemically induced. Accordingly, it is suggested that this distinctive renal tumor phenotype be recorded as a separate category from conventional RTT when assessing the carcinogenic potential of a test compound.

Key Words: rat • renal tubule tumors • spontaneous occurrence • amphophilic-vacuolar renal tumors • familial renal tumors

Abbreviations: ATH, atypical tubule hyperplasia • AV, amphophilic-vacuolar • CPN, chronic progressive nephropathy • H&E, hematoxylin and eosin • RTT, renal tubule tumor(s) • TEF, toxic equivalency factor • TDMS, Toxicology Data Management System

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