RITA—Registry of Industrial Toxicology Animal data: The application of historical control data for Leydig cell tumors in rats

Nolte, Thomas; Rittinghausen, Susanne; Kellner, Rupert; Karbe, E.; Kittel, Birgit; Rinke, Matthias; Deschl, Ulrich

doi:10.1016/j.etp.2010.05.006

Cited by 10 publications

(16 citation statements)

References 27 publications

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“…In other strains, much lower incidences have been reported from contract research organizations, that is, approximately 0.8% to 4% in SD and Wistar rats (Charles River 2004River , 2011Envigo 2016). Higher rates extracted from the Registry of Industrial Toxicology (RITA) database were reported by Nolte et al (2010) as 13.7% in Wistar-derived rat, continued breeding by Unilever (Nolte et al 2010). Most Leydig cell tumors are of a benign nature but may cause early sacrifice of the tumor bearers.…”

Section: Testesmentioning

confidence: 99%

Differences in Types and Incidence of Neoplasms in Wistar Han and Sprague-Dawley Rats

Weber¹

2017

Toxicol Pathol

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A substantial quantity of data on Sprague-Dawley (SD) and Hannover Wistar rats strains have been published concerning their source, diet, and housing conditions, as well as the incidences of nonneoplastic lesions and neoplasms observed in different laboratories. Differences between the commonly used rat strains provided by different breeders (i.e., CD (SD) vs. Harlan Sprague-Dawley strain or Crl: WI(Han) vs. Wistar Hannover (Han)-derived strain, continued breeding by RCC Ltd., Switzerland, thereafter continued breeding by Harlan) may include, but are not limited to, body weight, incidence, and onset of major nonneoplastic lesions and neoplasms, and these can impact the development of a nonclinical safety program. Fisher 344 (F344) and SD rat strains generally have the highest tumor incidences, exceeding that in Wistar rats. Certain tumors are more commonly observed in one strain, and for some, the difference in incidence may be so significant that the tumor may even be considered characteristic for a specific strain (e.g., thymoma in Wistar and amphophilic renal adenoma in SD).

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Section: Testesmentioning

confidence: 99%

Differences in Types and Incidence of Neoplasms in Wistar Han and Sprague-Dawley Rats

Weber¹

2017

Toxicol Pathol

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“…Leydig cell tubules have to be differentiated from hyperplasia and adenoma of the rete testis Rehm and Waalkes 1988). The spontaneous incidence of Leydig cell adenoma in rats seems to be inversely correlated to the body weight (Nolte et al 2010). Leydig cell hyperplasia and Leydig cell adenoma are readily induced in the rat by many xenobiotics from different chemical and therapeutic classes.…”

Section: Adenoma Leydig Cell (Figures 55-58): Testismentioning

confidence: 99%

Proliferative and Nonproliferative Lesions of the Rat and Mouse Male Reproductive System

Creasy

Bube

Rijk³

et al. 2012

Toxicol Pathol

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204

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The INHAND Project (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) is a joint initiative of the Societies of Toxicologic Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP), and North America (STP) to develop an internationally accepted nomenclature for proliferative and nonproliferative lesions in laboratory animals. The purpose of this publication is to provide a standardized nomenclature and differential diagnosis for classifying microscopic lesions observed in the male reproductive system of laboratory rats and mice, with color microphotographs illustrating examples of some lesions. The standardized nomenclature presented in this document is also available for society members electronically on the Internet (http://goreni.org). Sources of material included histopathology databases from government, academia, and industrial laboratories throughout the world. Content includes spontaneous and aging lesions as well as lesions induced by exposure to test materials. A widely accepted and utilized international harmonization of nomenclature for lesions of the male reproductive system in laboratory animals will decrease confusion among regulatory and scientific research organizations in different countries and provide a common language to increase and enrich international exchanges of information among toxicologists and pathologists.

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“…In rats, the incidence of LCH/LCTs varies between strains. LCH/LCTs are common in F344 rats (incidence: close to 100%), but are rare in SD rats (incidence: ranging from 1 to 5%) 5 . Although SDT rats are an inbred strain of SD rats, there is a high incidence of LCH/LCTs in SDT rats.…”

Section: Discussionmentioning

confidence: 99%

“…In rodents, Leydig cell tumors (LCT) are particularly common in F344 rats, but are less frequent in SD rats 5 . Spontaneously Diabetic Torii (SDT) rats, an inbred strain of SD rats, are a well-known non-obese type 2 diabetic model that achieve diabetic status with high plasma glucose levels by 42 weeks of age 6 .…”

Section: Introductionmentioning

confidence: 99%

Hyperglycemia contributes to the development of Leydig cell hyperplasia in male Spontaneously Diabetic Torii rats

et al. 2020

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Spontaneously Diabetic Torii (SDT) rats are a well-known animal model of non-obese type 2 diabetes mellitus. Although this animal model has been studied extensively over the last decade, the incidence rates of Leydig cell hyperplasia and tumors in this model have not been reported. In this study, pathophysiological analyses of the testes were performed on male SDT rats, to understand the effect of insulin treatment on the development of Leydig cell hyperplasia and tumors and the expression of integrins and extracellular matrix proteins. Testicular Leydig cell hyperplasia and tumors were observed in SDT rats at 64 weeks of age but were rarely identified in Sprague-Dawley (SD) rats of the same age. Insulin treatment decreased plasma glucose and HbA1c levels, and interestingly, decreased the number of hyperplastic Leydig cell foci and Leydig cell tumors in treated animals. A similar reduction in the expression of Ki67 in these Leydig cell foci was also observed. In addition, insulin treatment decreased the expression of integrin α5, integrin β1, integrin αvβ3, fibronectin, and vitronectin in hyperplastic Leydig cell foci. These results suggest that insulin might decrease the incidence of Leydig cell hyperplasia by reducing Leydig cell proliferation and the expression of integrins and extracellular matrix proteins through the reduction of serum glucose concentrations in these animals.

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RITA—Registry of Industrial Toxicology Animal data: The application of historical control data for Leydig cell tumors in rats

Cited by 10 publications

References 27 publications

Differences in Types and Incidence of Neoplasms in Wistar Han and Sprague-Dawley Rats

Differences in Types and Incidence of Neoplasms in Wistar Han and Sprague-Dawley Rats

Proliferative and Nonproliferative Lesions of the Rat and Mouse Male Reproductive System

Hyperglycemia contributes to the development of Leydig cell hyperplasia in male Spontaneously Diabetic Torii rats

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