Incidence of Nonneoplastic Lesions in Historical Control Male and Female Fischer-344 Rats from 90-Day Toxicity Studies

Dixon, Darlene; Heider, Katharina; Elwell, Michael R.

doi:10.1177/019262339502300310

Cited by 48 publications

(30 citation statements)

References 11 publications

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“…Lesions similar in morphology and location to those observed in this study have been reported in ad libitum-fed SpragueDawley rats (10) and in aging Fischer-344 rats (6).…”

Section: Introductionsupporting

confidence: 85%

Histopathological Evaluation of Liver, Pancreas, Spleen, and Heart from Iron-Overloaded Sprague-Dawley Rats*^1,2

et al. 1996

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The effects of increasing dietary levels of Fe on the histopathology of liver, pancreas, spleen, and heart were examined in a rat model for iron overload. Sprague-Dawley rats were fed diets containing 35, 350, 3,500, or 20,000 μg Fe/g, and, after 12 wk, there was a direct correlation between increased liver nonheme Fe and lipid peroxidation measured by the lipid-conjugated diene assay. Histopathological examination of tissues revealed the following: (a) hepatocellular hemosiderosis in all groups of rats, with a doserelated accumulation of cytoplasmic Fe-positive material predominantly in hepatocytes located in the periportal region (Zone 1), (b) myocardial degeneration and necrosis (cardiomyopathy) with hemosiderin in interstitial macrophages or in myocardial fibers of animals with heart damage, (c) splenic lymphoid atrophy affecting the marginal zone of the white pulp and hemosiderin deposition in the sinusoidal macrophages, and (d) pancreatic atrophy with loss of both the endocrine and exocrine pancreatic tissue in those animals receiving 3,500 and 20,000 μg Fe/g of diet. The toxic effects of Fe overload in this rat model include cellular apoptosis or necrosis in heart, spleen, and pancreas and, when coupled with the findings on lipid peroxidation, suggests that oxidative stress is involved in the pathogenesis of the lesions.

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“…Lesions similar in morphology and location to those observed in this study have been reported in ad libitum-fed SpragueDawley rats (10) and in aging Fischer-344 rats (6).…”

Section: Introductionsupporting

confidence: 85%

Histopathological Evaluation of Liver, Pancreas, Spleen, and Heart from Iron-Overloaded Sprague-Dawley Rats*^1,2

et al. 1996

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“…Heterogenous clusters of differentiated erythroid and/or myeloid cells located in the adipose tissue and interstitium adjacent to the renal pelvis Do not invade or replace existing renal tissue Differential diagnosis lymphoma or leukemia: homogenous group of cells with invasive characteristics more often extending into and replacing renal parenchyma Comment: The major toxicologic significance of renal extramedullary hematopoiesis is in the suggestion of the presence of a regenerative anemia and/or erythroid or myeloid stimulation (Dixon, Heider, and Elwell 1995;Pospisil et al 1998). …”

Section: Diagnostic Featuresmentioning

confidence: 99%

Proliferative and Nonproliferative Lesions of the Rat and Mouse Urinary System

et al. 2012

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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 for classifying lesions observed in the urinary tract of rats and mice. The standardized nomenclature of urinary tract lesions presented in this document is also available electronically on the Internet (http://www.goreni.org/). Sources of material included histopathology databases from government, academia, and industrial laboratories throughout the world. Content includes spontaneous developmental and aging lesions as well as those induced by exposure to test materials. A widely accepted and utilized international harmonization of nomenclature for urinary tract lesions 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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“…This proliferating lesion is often referred to as deciduoma and is thought to be a proliferative response of stromal endometrial cells that is histologically similar to decidual implantation sites 2 . This change is infrequently seen in young adult rats used in subacute toxicity studies, and the incidence of decidual reactions/deciduoma in young female F344 rats examined in National Toxicity Program studies is 1.3% (2 of 159 rats) 12 . Only 5 spontaneous cases of decidual reactions/deciduoma were identified in approximately 12000 Sprague-Dawley (SD) rats at 3- to 8-months of age 13 .…”

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confidence: 98%

Histopathological and Immunohistochemical Characterization of Spontaneously Occurring Uterine Deciduomas in Young Adult Rats

et al. 2013

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Uterine deciduomas were found in two female virgin rats, a 15-week-old Lewis rat and a 7-week-old Sprague-Dawley rat. The firm white nodules were located at the base of unilateral uterine horns and were approximately 6 mm and 4 mm in diameter. Histopathologically, the nodules were composed of three areas, each with a distinct type of proliferating cells: large epithelioid decidual cells with round nuclei, prominent nucleoli and abundant eosinophilic cytoplasm (antimesometrial region); compact spindle-shaped cells with oval nuclei and vacuolar cytoplasm (transitional region); and pleomorphic and spiny cells with round to oval nuclei and compact eosinophilic cytoplasm (mesometrial region). These cells proliferated in sheet-like arrangements and transformed into the other types of cells located in surrounding regions. Immunohistochemically, proliferating cells in all regions were strongly positive for proliferating cell nuclear antigen. The proliferating cells were positive for vimentin, and large decidual cells were positive for common acute lymphoblastic leukemia antigen 10, a marker of uterine interstitial cells. Large decidual cells were positive for α-smooth muscle actin and desmin, suggesting differentiation into muscular cells. Progesterone receptor was expressed in all cell types; however, estrogen receptor α was not expressed in the antimesometrial region. These extremely rare tumor-like nodules represent nonneoplastic lesions referred as decidual reactions of endometrial interstitial cells, and their biological behavior is that of a space-occupying benign tumor in young rats. Our cases might provide information as a historical control in toxicity and pharmacological studies in rats.

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Incidence of Nonneoplastic Lesions in Historical Control Male and Female Fischer-344 Rats from 90-Day Toxicity Studies

Abstract: The incidence of all spontaneously occurring histologic lesions was determined for control (F-344) rats from 90-day (13-wk)

Cited by 48 publications

References 11 publications

Histopathological Evaluation of Liver, Pancreas, Spleen, and Heart from Iron-Overloaded Sprague-Dawley Rats*^1,2

Histopathological Evaluation of Liver, Pancreas, Spleen, and Heart from Iron-Overloaded Sprague-Dawley Rats*^1,2

Proliferative and Nonproliferative Lesions of the Rat and Mouse Urinary System

Histopathological and Immunohistochemical Characterization of Spontaneously Occurring Uterine Deciduomas in Young Adult Rats

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Incidence of Nonneoplastic Lesions in Historical Control Male and Female Fischer-344 Rats from 90-Day Toxicity Studies

Abstract: The incidence of all spontaneously occurring histologic lesions was determined for control (F-344) rats from 90-day (13-wk)

Cited by 48 publications

References 11 publications

Histopathological Evaluation of Liver, Pancreas, Spleen, and Heart from Iron-Overloaded Sprague-Dawley Rats*1,2

Histopathological Evaluation of Liver, Pancreas, Spleen, and Heart from Iron-Overloaded Sprague-Dawley Rats*1,2

Proliferative and Nonproliferative Lesions of the Rat and Mouse Urinary System

Histopathological and Immunohistochemical Characterization of Spontaneously Occurring Uterine Deciduomas in Young Adult Rats

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Histopathological Evaluation of Liver, Pancreas, Spleen, and Heart from Iron-Overloaded Sprague-Dawley Rats*^1,2

Histopathological Evaluation of Liver, Pancreas, Spleen, and Heart from Iron-Overloaded Sprague-Dawley Rats*^1,2