This Article Free Full Text (Free PDF) Free References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Nyska, A. Articles by Maronpot, R. R. Search for Related Content PubMed PubMed Citation Articles by Nyska, A. Articles by Maronpot, R. R. Pubmed/NCBI databases Medline Plus Health Information Adrenal Gland Cancer Pheochromocytoma Social Bookmarking                         What's this?

The Association Between Severe Nephropathy and Pheochromocytoma in the Male F344 Rat— The National Toxicology Program Experience

National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA, Nyska{at}niehs.nih.gov

Joseph K. Haseman

National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA

James R. Hailey

National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA

Samuel Smetana

Nephrology Institute, Wolfson Medical Center, Holon 58100, Israel

Robert R. Maronpot

National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA

The possible correlation between the severity of chronic progressive glomerulonephropathy (CPN) and the incidence of adrenal pheochromocytoma was examined in selected studies of male Fischer 344 (F344) rats at the National Toxicology Program (NTP). The NTP historical control database was first examined in order to determine whether there was association between the severity of CPN and the occurrence of adrenal pheochromocytoma in unexposed animals. Following this analysis, the 125 most recent NTP studies conducted in F344 rats were examined in order to determine how frequently chemicals that cause increased severity of CPN showed an increased incidence of pheochromocytoma. Finally, we examined the association between the incidence of pheochromocytoma and the severity of CPN in those NTP studies with chemically related increased rates of pheochromocytoma. In control male F344 rats surviving beyond 21 mo, the incidence of adrenal pheochromocytoma was consistently higher in animals with more severe CPN. This association was significant (p < 0.05) both for 900 NTP inhalation study controls and 900 NTP feeding study controls. An association was not consistently observed when dosed groups were considered. Although 22% (28/125) of NTP studies reported a chemically related increased severity of CPN, only 3 of these reported a corresponding significant increase in the incidence of pheochromocytoma. Of 6 NTP studies that reported increased incidence of pheochromocytoma, animals with pheochromocytoma from 5 of those studies had some degree of increased severity of CPN. However, the estimated strength of the correlation with the severity of CPN varied from study to study and was often quite different from that indicated by an analysis of the more extensive NTP control databases. The possible correlation between the severity of CPN and the incidence of pheochromocytoma may influence interpretation of carcinogenic effects observed at this site.

Key Words: Rat adrenal medullary tumors • glomerulonephropathy • calcium • nongenotoxic • carcinogenicity

Toxicologic Pathology, Vol. 27, No. 4, 456-462 (1999)
DOI: 10.1177/019262339902700410


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				J. K. Haseman, E. Ney, A. Nyska, and G. N. Rao Effect of Diet and Animal Care/Housing Protocols on Body Weight, Survival, Tumor Incidences, and Nephropathy Severity of F344 Rats in Chronic Studies Toxicol Pathol, October 1, 2003; 31(6): 674 - 681. [Abstract] [PDF]

				K. Ozaki, J. K. Haseman, J. R. Hailey, R. R. Maronpot, and A. Nyska Association of Adrenal Pheochromocytoma and Lung Pathology in Inhalation Studies with Particulate Compounds in the Male F344 Rat--The National Toxicology Program Experience Toxicol Pathol, February 1, 2002; 30(2): 263 - 270. [Abstract] [PDF]

				T. J. Rosol, J. T. Yarrington, J. Latendresse, and C. C. Capen Adrenal Gland: Structure, Function, and Mechanisms of Toxicity Toxicol Pathol, January 1, 2001; 29(1): 41 - 48. [Abstract] [PDF]