A total of 93 tumors of the epidermis, its appendages, and dermis were observed in 1,433 (717 males, 716 females) rats employed in oncogenicity studies over a 2-yr period. Mammary gland neoplasms will be reported separately. Fifty-seven (61.3%) were epithelial with 49 in males and 8 in females. Keratoacanthoma was the most frequent epithelial neoplasm in males (22) followed by squamous cell carcinoma (11) and papilloma (5). Sebaceous gland neoplasms seen in males (5) included both adenomas (3) and carcinomas (2). In males, there were also 3 trichoepitheliomas, 1 pilomatricoma, 1 basal cell tumor, and 1 malignant melanoma. Of the 8 epithelial neoplasms in females, there were 3 squamous cell carcinomas, 2 keratoacanthomas, and 1 each basal cell tumor, malignant melanoma, and trichoepithelioma. There were 21 mesenchymal neoplasms in males and 15 in females. The most frequent neoplasm was fibroma (7 males, 8 females) followed by lipoma (7 males, 4 females) and fibrosarcoma (4 males, 3 females). One male had a liposarcoma and 2 males each had hemangioma. The total neoplasm incidence of 70/717 (9.8%) in males and 23/716 (3.2%) in females showed that skin neoplasms were 3 time more common in males than in females. Epithelial neoplasms of the skin were 6 times more common in males than in females. Males were more than twice as likely to have epithelial rather than mesenchymal skin neoplasms whereas the reverse was seen in females.
Primary malignant neoplasms of the brain and spinal cord occurred in 20/718 male (2.8%) and in 13/717 female (1.8%) Crl:CD®Br strain Sprague-Dawley rats. Of 33 neoplasms, 30 were found in brain while 3 were in the spinal cord. In males and females, the most common brain neoplasm was astrocytoma (13 males, 9 females). Other neoplasms, granular cell tumor (1 male), mixed glioma (2 males, 1 female), reticulosis (1 male, 2 females), and oligodendroglioma (2 males), were especially uncommon. Spinal cord neoplasms included 2 schwannomas (1 male, 1 female) and an astrocytoma (1 male). The overall brain neoplasm incidence was similar for males (2.8%) compared to data compiled for this strain, and there was a 2-fold increase for females (1.8% vs 0.9%) compared to available incidence data.
Primary benign and malignant vascular neoplasms occurred spontaneously in 8 of 710 male (1.1%) and 4 of 710 female (0.6%) CrI:CD®Br strain Sprague-Dawley rats employed in two 2-yr oncogenicity studies (1,400) and as controls in a 1-yr toxicity study (20). Four of 13 neoplasms were found in the spleen; skin and kidney each had 2 neoplasms. Single vascular neoplasms were in the liver, testicle, uterus, mesenteric lymph node, and vagina. Hemangioma was more common (5 males, 2 females) than hemangiosarcoma (3 males, 2 females). Vascular neoplasms were considered the cause of death in 2 females, both with hemangiosarcomas involving the spleen or kidney. One male had 2 primary hemangiomas in separate organs. Vascular neoplasms are infrequently reported [1/82 females (1.2%), 1961; 9/880 both sexes (1.0%), 1985] in this rat strain. The incidence of vascular neoplasms of this report was higher in males (9) than in females (4), in contrast to incidences reported in the literature.
Corticosteroids have for many years proven beneficial in the necessary treatment of diseases and conditions that respond to their anti-inflammatory, immunosuppressive, or hormonal effects. Deflazacort is a derivative of prednisolone and is currently used in humans. Deflazacort was fed in the diet for 1 yr to Crl:CD BR rats at doses from 0.03 to 1.0 mg/kg/day to evaluate its toxic potential. Deflazacort-induced pancreatic islet cell hyperplasia in the 1-yr study was evaluated using subjective and objective methods on routine hematoxylin-and-eosin- or peroxidase-anti-peroxidase-stained preparations of pancreas (islets); the relationship of blood glucose and serum insulin levels to doses of deflazacort administered to rats was also examined. Diagnostic electron microscopy was conducted on similar proliferative islet lesions for a few high-dose males of a parallel carcinogenicity study. This study revealed that proliferative islet lesions were comprised mainly of beta cells (insulin producing) and that the islet area correlated well with hyperplasia grade and dose. However, there were no statistically significant relationships among reductions in blood glucose, serum insulin concentration, and proliferative islet alterations.
Primary neoplasms of the kidneys occurred in 11/682 male (1.6%) and 2/694 female (0.3%) Crl:CD®Br strain Sprague-Dawley rats. Eight of 13 neoplasms were of mesenchymal origin and 5 of 13 were epithelial. Five neoplasms were lipoma (3) or liposarcoma (2). Three of 13 were either hemangioma (1) or mesenchymal tumors (2). The epithelial neoplasms were carcinomas. There was no microscopic evidence of metastasis among those neoplasms judged malignant on morphologic criteria. The overall natural incidence in males was nearly double that compiled for this strain while in females the incidence was similar to that reported for other females.Keywords. Epithelial; mesenchymal; benign; malignant; Sprague-Dawley Primary spontaneous neoplasms of the kidney are uncommon (0.4% to -1.0%) in rats and, like other neoplasm incidences, reach peak only near the end of 2-yr oncogenicity or lifespan studies (4, 6-8, 18, 19, 21, 22, 24, 25). However, in one report, renal neoplasm incidences in Sprague-Dawley rats from 2 different sources ranged from 4.9-26.4% (1). Both epithelial and mesenchymal neoplasms have been induced in rats by chemical agents (1-3, 9, 11-15, 20, 23) Mesenchymal tumors were large disfiguring neoplasms (Fig. la) tumors were characterized by a distinct lack of structure ( Fig. 1 b, (Fig. 2a). These neoplasms were diagnosed at an average age of 679 (565-737) test days, consistent with older rat involvement reported elsewhere (10), and all were incidental. Carcinomas were comprised of anaplastic epithelial cells with pleomorphic nuclei and numerous mitoses (Fig. 2b). Another type of carcinoma was comprised of clear staining cells arranged in cords or abortive tubules (Fig. 3a, b While primary renal neoplasia occurred infrequently in rats of this report, the incidence in males was 5-fold greater than in females. Although a variety of agents can induce renal neoplasia, the reason(s) for an apparent increase of spontaneous renal neoplasms in males here (1.6%), relative to previously reported incidences (0.4-1.0%), excluded corticosteroid treatment and is unknown. It is, however, important to be aware of shifts in the spontaneous incidence for the evaluation and interpretation of carcinogenic responses in oncogenicity studies using this strain from the same or different sources. ACKNOWLEDGMENTS
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