Spontaneous neoplasms in aged Sprague-Dawley rats

Wilbur G. Toxicology Laboratories, American Cyanamid Company, Pearl River, NY 10965.
Archive für Toxikologie (Impact Factor: 5.98). 02/1992; 66(7):496-502. DOI: 10.1007/BF01970675
Source: PubMed


Incidence of neoplastic lesions in untreated Sprague-Dawley rats (1340 males and 1329 females) used as controls in 17 carcinogenicity studies are tabulated and evaluated. In male rats, the most common neoplasms were benign pheochromocytomas and keratoacanthomas (4.0% in each case) followed by pancreatic islet cell adenomas (3.7%), thyroid parafollicular cell adenomas (3.6%), fibromas and squamous cell papillomas of the skin and hepatocellular adenomas (2.0% in each), malignant lymphoma lymphocytic (1.9%), histiocytic sarcomas (1.4%), and adrenal cortical adenomas (1.2%). In female rats, the most common neoplasms were of mammary gland origin (31.3%: fibroadenoma 19.0%, adenocarcinomas 8.8%, and adenomas 3.5%) followed by thyroid parafollicular cell adenomas (2.9%), uterine endometrial stromal polyps (2.6%), adrenal cortical adenomas (1.9%), malignant lymphoma lymphocytic (1.6%), fibromas in the skin (1.3%), and pancreatic islet cell adenoma (1.1%). Metastases were observed from pheochromocytomas, hepatocellular carcinomas, nephroblastomas, renal pelvis transitional cell carcinoma, interstitial cell tumor and seminoma of the testes, Zymbal's gland adenocarcinomas, and mammary adenocarcinomas.

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Available from: Dale Johnson, Jun 12, 2014
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    • "The mean for LC adenomas in the Charles River compilation, comprising 2146 male SD rats, is with 2.4% also in this range (Giknis and Clifford 2004). A considerably lower mean incidence of 0.8% was reported in 1340 SD rats (Chandra et al. 1992). The maximum incidence of 10% found in a RITA study was comparable to the maximum incidence of 9.33% in the Charles River compilation. "
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    ABSTRACT: Historical data for Leydig cell tumors from untreated or vehicle treated rats from carcinogenicity studies collected in the RITA database are presented. Examples are given for analyses of these data for dependency on variables considered to be of possible influence on the spontaneous incidence of Leydig cell tumors. In the 7453 male rats available for analysis, only one case of a Leydig cell carcinoma was identified. The incidence of Leydig cell adenomas differed markedly between strains. High incidences of close to 100% have been found in F344 rats, while the mean incidence was 4.2% in Sprague-Dawley rats and 13.7% in Wistar rats. Incidences in Wistar rats were highly variable, primarily caused by different sources of animals. Mean incidences per breeder varied from 2.8 to 39.9%. Analyses for the dependency on further parameters have been performed in Wistar rats. In breeders G and I, the Leydig cell tumor incidence decreased over the observation period and with increasing mean terminal body weight. The incidence of Leydig cell tumors increased with mean age at necropsy and was higher in studies with dietary admixture compared to gavage studies. These parameters had no effect on Leydig cell tumor incidence in breeders A and B. Animals from almost all breeders had a considerably higher mean age at necropsy when bearing a Leydig cell adenoma than animals without a Leydig cell adenoma. Studies with longitudinal trimming of the testes had a higher incidence than studies with transverse trimming. The observed dependencies and breeder differences are discussed and explanations are given. Consequences for the use of historical control data are outlined. With the retrospective analyses presented here we were able to confirm the published features of Leydig cell adenomas and carcinomas. This indicates that the RITA database is a valuable tool for analyses of tumors for their biological features. Furthermore, it demonstrates that the RITA database is highly beneficial for the definition of reliable historical control data for carcinogenicity studies on a scientifically solid basis.
    Full-text · Article · Nov 2011 · Experimental and toxicologic pathology: official journal of the Gesellschaft fur Toxikologische Pathologie
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    • "Adenocarcinoma of the salivary glands, a very rare tumor even in aged rats2,4, was seen in one 32-week-old male rat, indicating the difficulty of showing an age-related tendency in the occurrence of very rare tumors. "
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    ABSTRACT: It is important for the assessment of toxicological effects of chemicals to know what kinds of neoplasms naturally occur in the early life of experimental animals. In the present study, we demonstrated spontaneous neoplasms in Sprague-Dawley rats used in 4-, 13- and 26-week toxicity studies conducted at Bozo Research Center in the last decade. The tumors, which were first observed in 19-week-old animals, included anterior adenoma of the pituitary, follicular cell adenocarcinoma and C cell adenoma of the thyroids, nephroblastoma of the kidneys, basal cell tumor of the skin and malignant lymphoma. Thereafter, hemangiosarcoma of the tongue, adenocarcinoma of the submandibular glands, histiocytic sarcoma of the spleen, oligodendroglioma of the brain and adenocarcinoma and fibroadenoma of the mammary glands were detected in 32-week-old animals. The incidences of mammary adenocarcinoma and pituitary anterior adenoma were higher than those of other tumors. The present results showed that the same tumors as reported in aged rats could also develop in younger rats.
    Full-text · Article · Mar 2011 · Journal of Toxicologic Pathology
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    • "Pituitary gland adenomas and mammary gland neoplasms are recognized as the most common spontaneous neoplasms in female SD rats (Chandra, Riley, and Johnson 1992; Ettlin, Stirnimann, and Prentice 1994; McMartin et al. 1992; Son 2004). Pituitary gland adenomas produce multiple hormones, including prolactin, which is implicated in the development of mammary gland neoplasms (Attia 1985; McComb et al. 1984). "
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    ABSTRACT: The National Toxicology Program (NTP) has historically used Fischer 344/N (F344/N) rats for the majority of its bioassays. Recently the NTP began using the Harlan Sprague Dawley (SD) as the primary rat model for NTP studies. The NTP had previously used female SD rats in nine bioassays. This article compares historical control (HC) tumor incidence rates from these nine SD rat studies with HC tumor rates from matched NTP F344/N rat bioassays to identify similarities and differences. Matching on sex, laboratory, diet, and route led to nine comparable F344/N rat studies. Our analyses revealed statistically significant strain differences, with female SD rats having lower incidence rates for clitoral gland adenoma (0.2% vs. 5.8%) and mononuclear cell leukemia (0.9% vs. 16.7%) and higher incidence rates for mammary gland fibroadenoma (67.4% vs. 48.4%), mammary gland carcinoma (10.2% vs. 2.4%), and thyroid gland C cell adenoma (25.4% vs. 13.6%) relative to female F344/N rats. These represent five of the seven most common tumor types among female SD and F344/N rats in the NTP HC database. When vehicle was included as an additional matching criterion, the number of comparable F344/N rat studies dropped to four, but similar results were obtained.
    Full-text · Article · Aug 2010 · Toxicologic Pathology
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