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Bradley A.,Charles River Edinburgh | Mukaratirwa S.,Charles River Edinburgh | Petersen-Jones M.,Charles River Edinburgh
Toxicologic Pathology | Year: 2012

The authors performed a retrospective study to determine the incidences and range of spontaneous pathology findings in the lymphoid and haemopoietic systems of control Charles River CD-1 mice (Crl: CD-1(ICR) BR). Data was collected from 2,560 mice from control dose groups (104-week and 80-week carcinogenicity studies; 13-week studies), from regulatory studies evaluated at the authors' laboratory between 2005 and 2010. Lesions of the lymphoid and hematopoietic systems were uncommon in 13-week studies but were of high incidence in the carcinogenicity studies (80- or 104-week duration). The most common finding overall was lymphoid hyperplasia within the spleen, thymus, and lymph nodes. The finding of benign lymphoid hyperplasia of the thymus is unusual in other mouse strains. The most common cause of death in the carcinogenicity studies was lymphoma. It is hoped that the results presented here will provide a useful database of incidental pathology findings in CD-1 mice on carcinogenicity studies. © 2012 Society of Toxicologic Pathology.


Petterino C.,Charles River Edinburgh | Mukaratirwa S.,Charles River Edinburgh | Bradley A.,Charles River Edinburgh
Toxicology Letters | Year: 2015

The authors performed a retrospective study to determine the incidences and range of spontaneous lesions in the bone marrow (sternum and femur) of control mice and rats. Data was collected from 2186 mice (Crl:CD-1(ICR)BR), and 2347 rats (Han Wistar and CD(SD) rats) from the control dose groups of 104-week carcinogenicity studies carried out between 2005 and 2014. The incidence of spontaneous lesions in the bone marrow was higher in mice than in rats, and in both species non-neoplastic lesions were more common than neoplastic lesions. In mice, the most common non-neoplastic lesions in the bone marrow were increased cellularity, pigmented macrophages, and decreased cellularity, and the most common neoplastic lesions were malignant lymphoma, granulocytic leukemia and histiocytic sarcoma. There were occasional sex and site differences (sternum marrow vs femur marrow) in the incidence of a few bone marrow lesions in mice. In rats, the most common non-neoplastic lesions were increased cellularity and stromal fibrosis, and the most common neoplastic lesion was malignant lymphoma. In rats, no sex predilection in the incidence of bone marrow lesions was apparent, and there were no significant site differences in the incidence of lesions. To the best knowledge of the authors, there are no recent reports on spontaneous pathological findings in bone marrow of rodents, and we believe that these results will facilitate the interpretation of background findings and/or their increased incidence in carcinogenicity studies. © 2015 Elsevier Ireland Ltd.


Chamanza R.,Charles River Edinburgh | Marxfeld H.A.,Charles River Edinburgh | Blanco A.I.,Charles River Edinburgh | Naylor S.W.,Charles River Edinburgh | Bradley A.E.,Charles River Edinburgh
Toxicologic Pathology | Year: 2010

The authors performed a retrospective study to determine the incidences and range of spontaneous pathology findings in control cynomolgus monkeys. Data were collected from 570 monkeys (285 animals per sex), aged twelve to thirty-six months, from sixty regulatory studies evaluated at our laboratory between 2003 and 2009. The most common finding overall was lymphoplasmacytic infiltrates observed in the following incidence: liver (60.7%), kidneys (28.8%), heart (25.8%), salivary glands (21.2%), and stomach (12.1%). Inflammation also commonly occurred in the heart, kidneys, lungs, and stomach. The most common degenerative changes were localized fatty change in the liver, myocardial degeneration, and mineralization and pigment deposits in various tissues. Parathyroid, thyroid, and pituitary cysts; ectopic thymus in the parathyroid or thyroid gland; accessory spleen within the pancreas; and adrenohepatic fusion were among the most common congenital findings. Some incidental findings bearing similarities to drug-induced lesions were also encountered in various organs. It is hoped that the results presented here and elsewhere could form the groundwork for the creation of a reliable database of incidental pathology findings in laboratory nonhuman primates. Copyright © 2010 by The Author(s).


Rehg J.E.,St Jude Childrens Research Hospital | Rahija R.,St Jude Childrens Research Hospital | Bush D.,St Jude Childrens Research Hospital | Bradley A.,Charles River Edinburgh | Ward J.M.,Global Vet Pathology
Toxicologic Pathology | Year: 2015

A few reports indicated the incidence of hematolymphoid neoplasms in old CD-1 mice, but the cellular lineage of CD-1 mouse neoplasms has not been published. In this study, immunohistochemistry (IHC) was used to characterize the cellular lineage of spontaneous hematolymphoid neoplasms arising in 24 young female CD-1 mice used as health-monitoring sentinels and 32 aging female CD-1 mice used as controls in 80-week carcinogenesis studies. Lymphoblastic lymphomas of T-cell and B-cell lineage were common in mice aged 12 months or less, whereas a wide range of non-lymphoblastic B-cell lymphomas and lymphoblastic B-cell lymphomas were common in mice >12-mo-old. Renal hyaline droplets positive for lysozyme were observed in aged mice with a histiocytic-associated large B-cell lymphoma (HA-BCL) and a myeloid leukemia. Endogenous ecotropic mouse leukemia virus (MuLV) genes have been recovered from CD-1 mice, but MuLV protein expression has not been previously demonstrated. We reported for the first time the expression of a MuLV protein p30 by IHC in lymphomas and some normal tissues of both young and aging CD-1 mice. This report should help to differentiate spontaneous lymphomas and leukemias in CD-1 mice from those induced by chemicals and other methods. © 2015 by The Author(s).


PubMed | Charles River Edinburgh
Type: Journal Article | Journal: Toxicology letters | Year: 2015

The authors performed a retrospective study to determine the incidences and range of spontaneous lesions in the bone marrow (sternum and femur) of control mice and rats. Data was collected from 2186 mice (Crl:CD-1(ICR)BR), and 2347 rats (Han Wistar and CD(SD) rats) from the control dose groups of 104-week carcinogenicity studies carried out between 2005 and 2014. The incidence of spontaneous lesions in the bone marrow was higher in mice than in rats, and in both species non-neoplastic lesions were more common than neoplastic lesions. In mice, the most common non-neoplastic lesions in the bone marrow were increased cellularity, pigmented macrophages, and decreased cellularity, and the most common neoplastic lesions were malignant lymphoma, granulocytic leukemia and histiocytic sarcoma. There were occasional sex and site differences (sternum marrow vs femur marrow) in the incidence of a few bone marrow lesions in mice. In rats, the most common non-neoplastic lesions were increased cellularity and stromal fibrosis, and the most common neoplastic lesion was malignant lymphoma. In rats, no sex predilection in the incidence of bone marrow lesions was apparent, and there were no significant site differences in the incidence of lesions. To the best knowledge of the authors, there are no recent reports on spontaneous pathological findings in bone marrow of rodents, and we believe that these results will facilitate the interpretation of background findings and/or their increased incidence in carcinogenicity studies.


PubMed | Global Vet Pathology, St Jude Childrens Research Hospital and Charles River Edinburgh
Type: Journal Article | Journal: Toxicologic pathology | Year: 2015

A few reports indicated the incidence of hematolymphoid neoplasms in old CD-1 mice, but the cellular lineage of CD-1 mouse neoplasms has not been published. In this study, immunohistochemistry (IHC) was used to characterize the cellular lineage of spontaneous hematolymphoid neoplasms arising in 24 young female CD-1 mice used as health-monitoring sentinels and 32 aging female CD-1 mice used as controls in 80-week carcinogenesis studies. Lymphoblastic lymphomas of T-cell and B-cell lineage were common in mice aged 12 months or less, whereas a wide range of non-lymphoblastic B-cell lymphomas and lymphoblastic B-cell lymphomas were common in mice >12-mo-old. Renal hyaline droplets positive for lysozyme were observed in aged mice with a histiocytic-associated large B-cell lymphoma (HA-BCL) and a myeloid leukemia. Endogenous ecotropic mouse leukemia virus (MuLV) genes have been recovered from CD-1 mice, but MuLV protein expression has not been previously demonstrated. We reported for the first time the expression of a MuLV protein p30 by IHC in lymphomas and some normal tissues of both young and aging CD-1 mice. This report should help to differentiate spontaneous lymphomas and leukemias in CD-1 mice from those induced by chemicals and other methods.

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