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The Effect of Chronic Progressive Nephropathy on the Incidence of Renal Tubule Cell Neoplasms in Control Male F344 Rats

Experimental Pathology Laboratories, Inc, Research Triangle Park, North Carolina, seely1{at}niehs.nih.gov

Joseph K. Haseman

Laboratory of Computational Biology and Risk Analysis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina

Abraham Nyska

Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina

Douglas C. Wolf

Environmental Carcinogenesis Division, NHEERL, ORD, U.S. EPA, Research Triangle Park, North Carolina

Jeffrey I. Everitt

CT Centers for Health Research, Research Triangle Park, North Carolina

James R. Hailey

Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina

Chronic progressive nephropathy (CPN) is the most frequently diagnosed lesion in the rat kidney. It has many component s including degeneration and regeneration of renal tubule (RT) epithelium, glomerular lesions and interstitial inflammation and fi brosis. The incidence and severity of CPN is strain, age, and sex dependent and may be altered by a number of factors including exposure to xenobiotics. In National Toxicology Program (NTP) 2-year bioassays, xenobiotic-associated increased severity (exacerbation) of CPN often occurs in association with a marginal increased incidence of renal tubule cell neoplasms (RTCN). The relationship between CPN and RTCN development has not been defi nitively determined. The present study evaluated the association between severity of CPN and the occurrence of RTCN in control male F344 rats. A slight but statistically signifi cant increase in CPN severity was present in those animals with RTCN compared to aged-matched controls without RTCN. Although these data suggest there is a positive correlation between CPN and RTCN, cause and effect were not determined. This marginal association suggests that the number of RTCNs that may develop secondary to chemically exacerbated nephropathy would be few.

Key Words: Kidney • nephropathy • neoplasia • males • Fischer 344 rat • National Toxicology Program.

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