Occurrence of Spontaneous Amphophilic-Vacuolar Renal Tubule Tumors in Sprague-Dawley Rats from Subchronic Toxicity Studies

The low background incidence of tumors in rodents from subchronic toxicity studies makes it difficult to assess their relevance, especially when present only in treated animals. This report investigates the occurrence of renal tubule tumors (RTTs), specifically the amphophilic-vacuolar (AV) phenotyp...

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Bibliographic Details
Published in:	Toxicologic pathology Vol. 41; no. 6; pp. 866 - 871
Main Authors:	Crabbs, Torrie A., Frame, Steve R., Laast, Victoria A., Patrick, Daniel J., Thomas, Johnson, Zimmerman, Bevin, Hardisty, Jerry F.
Format:	Journal Article
Language:	English
Published:	Los Angeles, CA SAGE Publications 01-08-2013 Sage Publications
Subjects:	Animals Biological and medical sciences Female Histocytochemistry Kidney - pathology Kidney Neoplasms - pathology Kidney Neoplasms - veterinary Kidney Tubules - pathology Kidneys Male Medical sciences Multiple tumors. Solid tumors. Tumors in childhood (general aspects) Nephrology. Urinary tract diseases Rats Rats, Sprague-Dawley Rodent Diseases - pathology Toxicity Tests, Subchronic Toxicology Tumors Tumors of the urinary system familial renal tumors rat renal tubule tumors amphophilic-vacuolar renal tubule tumors spontaneous neoplasia Kidney disease Urinary system disease Subchronic Rat Family study Toxicity Spontaneous Kidney tumor Rodentia Malignant tumor Kidney Vertebrata Renal tubule Mammalia Urinary system Animal Family environment Cancer
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Summary:	The low background incidence of tumors in rodents from subchronic toxicity studies makes it difficult to assess their relevance, especially when present only in treated animals. This report investigates the occurrence of renal tubule tumors (RTTs), specifically the amphophilic-vacuolar (AV) phenotypic variant, in young Sprague-Dawley (SD) rats from a survey of laboratories conducting subchronic toxicity studies spanning a period of 10 years (2002–2012). This survey establishes a general profile of tumor occurrence; it does not estimate overall incidence or prevalence. AV tumors are spontaneous, nontreatment-related tumors of familial origin, and morphologically distinct from conventional RTTs induced by exposure to renal carcinogens. They are composed of distinct lobules of large, round to polyhedral cells with vacuolated amphophilic to eosinophilic cytoplasm and prominent nucleoli. Data from five collaborating laboratories, representing 37 qualifying studies, are presented. In total, 58 renal tubule neoplasms were recorded in this data set. The AV tumor variant was reported more commonly than the conventional RTT (n = 45 and 13, respectively), and it was recorded in both experimental (n = 32) and control (n = 13) groups. AV tumors occurred more often in females (n = 34) than in males (n = 11); conventional RTTs were recorded more often in males (n = 9) than in females (n = 4). AV tumors often occurred in more than one rat within the same study (up to 7) and were documented to occur in rats as young as 7 to 10 weeks of age. Results from this survey indicate that AV tumors are being reported more commonly in recent years; the majority (n = 33) were reported in studies commencing since 2009. In conclusion, this study reaffirms that AV tumors are spontaneous, nontreatment-related lesions, and suggests that they may be more common than conventional RTTs in young SD rats. The authors propose that AV tumors be recorded separately from conventional RTTs in order to clearly distinguish these two renal tubule neoplasms from one another and allow for appropriate interpretation of a compound’s potential carcinogenic effect in the kidney.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0192-6233 1533-1601
DOI:	10.1177/0192623312467523