Epididymal interstitial (Leydig) cell tumors in B6C3F1 mice

Six primary interstitial cell tumors of the epididymis were identified from 46,752 male B6C3F1 mice used in chronic toxicity and carcinogenicity studies. Five of the tumors occurred at the end of 2-year studies; none were attributed to treatment. None of the mice with epididymal tumors had a primary testicular tumor. Histologically, tumors were characterized by a nodular or diffuse proliferation of tumor cells in the epididymal interstitium. Most cells were polygonal with highly vacuolated cytoplasm (vacuolated cells) or eosinophilic cytoplasm (eosinophilic cells). Smaller hyperchromatic cells with scant basophilic cytoplasm (basophilic cells) and cells with yellow-brown pigment characteristic of lipofuscin (pigmented cells) were less common. In each tumor two or more cell types were present. Extension of these tumors through the capsule, invasion of the testis, or metastasis did not occur. By electron microscopy both eosinophilic and vacuolated cell types had a large round or oval nucleus with sparse heterochromatin, abundant mitochondria with tubulovesicular cristae, and frequent desmosome structures between cell membranes. Vacuolated cells contained numerous lipid droplets. Morphological features of the epididymal tumors are similar to those of the testicular interstitial (Leydig) cell tumor in mice and rats.     

Pathology of the mononuclear cell leukemia of Fischer rats. I. Morphologic studies

Pathological evaluations were done in 205 rats with mononuclear cell leukemia. Leukemia was diagnosed in 22.2% of males and 20.4% of females with significant risk beginning at 20 months of age. Mononuclear cell leukemia was responsible for 50% of early deaths in two-year studies. Clinically, rats became depressed, pale, icteric and had palpably enlarged spleens. Gross lesions included splenomegaly, enlarged mesenteric lymph nodes, and mottled livers. Hemorrhages occurred in the lungs, brain, and lymph nodes. Histological examination demonstrated that spleen and liver were most consistently and seriously involved, although numerous other organs contained leukemic infiltrates of variable severity. Spleens exhibited diffuse leukemic infiltration of the red pulp, follicular lymphoid depletion, and decrease in both extramedullary hematopoiesis and hemosiderin. Liver lesions consisted of diffuse centrilobular degeneration and necrosis. Erythrophagocytosis by tumor cells was common in the spleen and observed in liver, lymph nodes, and adrenals. The disease appeared to originate in the spleen. Bone marrow infiltration occurred late relative to spleen involvement and was present in less than half of the rats.     

Carcinogenicity and chronic toxicity in mice and rats exposed by inhalation to para-dichlorobenzene for two years

Carcinogenicity and chronic toxicity of para-dichlorobenzene (p-DCB) were examined by exposing 50 BDF1 mice and 50 F344 rats of both sexes by inhalation to p-DCB vapor at a target concentration of 0 (control), 20, 75 or 300 ppm for 6 hr/day, 5 days/week and 2 years. Incidences of hepatocellular carcinomas, hepatoblastomas and hepatic histiocytic sarcomas in the 300 ppm-exposed male mice, and hepatocellular adenomas and carcinomas and hepatoblastomas in the 300 ppm-exposed female mice were increased. An increase in the incidences of most of those liver tumors was dose-related. No increase in tumor incidence was found in any p-DCB-exposed rat of either sex. Centrilobular hypertrophy of hepatocytes and papillary mineralization and pelvic urothelial hyperplasia of the kidney were noted in the 300 ppm-exposed male rats. Treatment- and age-related increases in incidences of the eosinophilic globules of the respiratory and olfactory epithelia in female rats and incidences of the respiratory metaplasia of the nasal gland epithelium in mice and rats and the olfactory epithelium in mice were noted. The nasal lesion was the most sensitive endpoint of chronic inhalation toxicity. Induction of the mouse hepatocarcinogenicity and lack of the rat nephrocarcinogenicity found in the present study were compared with the mouse liver tumors and the rat renal tumors reported by the NTP gavage study, and discussed in light of the estimated p-DCB uptake into the body through the inhalation and the oral administration.     

Pathology of the mononuclear cell leukemia of Fischer rats. II. Hematology

Complete hemograms were evaluated for 57 rats with mononuclear cell leukemia and compared to hemograms obtained from 52 age- and sex-matched nonleukemic rats. All leukemic rats had marked hemolytic anemia and associated spherocytosis, reticulocytosis, anisocytosis, and polychromasia. The anemia varied with the stage of illness and was more severe in rts with advanced leukemia. Death appeared to be related to anemia. There was a marked neutrophilia with left shift, mild lymphopenia, and moderate to severe thrombocytopenia. Atypical mononuclear cells were detected in circulation in all but three rats. Total white blood cell counts ranged from 5.0-370 x 10(3) cells/ml. There was an increase in erythrocyte osmotic fragility with separation into two distinct populations of erythrocytes. Eight of nine rats were Coombs' positive indicating an immune-mediated pathogenesis for the anemia. Hemostasis tests revealed a markedly prolonged prothrombin time, hypofibrinogenemia, slightly increased to normal partial thromboplastin time, and undetected fibrin degradation products. These findings suggest significant liver disease associated with the leukemia.     

The influence of sex and gonadectomy on hepatic and brain fatty acid composition,lipogenesis and β‐oxidation

The aim of this study was to investigate the influence of sex and castration of rats on liver and brain fatty acid profile and liver mRNA expression of genes involved in lipogenesis and β‐oxidation. Castration significantly increased body weight and liver index and decreased serum triglyceride content in the female rats. The fatty acid composition of the liver tissue was influenced by sex and castration. Male rats had higher content of C16:0, C18:1n7, C18:2n6 and C22:5n3, while female rats had higher content of C18:0, C20:4n6 and C22:6n3. Castration of male rats decreased differences caused by sex for C18:2n6, C20:4n6 and C22:6n3. Values for C16:1n7 were higher in the castrated male rats in comparison with all other groups. Liver phospholipids showed a distribution of fatty acids similar to the total lipids. Brain total lipids and phospholipids were not influenced by sex or castration. Castration increased ?6D gene expression in both the sexes, while ?5D and ?9D increased in females and males respectively. Gonadectomy increased expression of the FASN gene in the females and decreased CPT1 and ACOX1 gene expression in the liver tissue of male rats. The observed results of lipid peroxidation, measured by TBARS, were the lowest in the intact females in comparison with all other groups. In conclusion, sex strongly influences both SFA and PUFA in liver tissue, and castration decreases these differences only for PUFA. Castration also influences the expression of the genes involved in lipid metabolism differently in male and female rats, with an increase in lipogenic genes in female rats and a decrease in key genes for mitochondrial and peroxisomal β‐oxidation in male rats.     

Hereditary polycystic kidney disease associated with osteorenal syndrome in rats

Hereditary polycystic kidney disease (PKD) was seen in Han:SPRD rats and identified as an autosomal, incomplete dominant trait. Homozygous animals died at 3 to 4 weeks of age, while heterozygous males were severely ill or moribund within about 6 months. Heterozygous females developed PKD to a lesser extent than males and survived longer. Renal secondary hyperparathyroidism and osteodystrophia fibrosa were seen in most males but were absent in females. In male rats metastatic calcification was found in kidneys, lungs, glandular and forestomach, blood vessels, and heart. In a few uremic males ulcerative enteritis occurred in cecum and colon. Blood urea nitrogen values were significantly increased in both sexes.     

Carcinogenicity of biphenyl in mice by two years feeding

Carcinogenicity and chronic toxicity of biphenyl was examined in the male and female BDF1 mice fed a diet containing biphenyl at 667, 2,000 or 6,000 ppm for 2 years. There was no difference in survival rate between any biphenyl-containing diet-fed group of either sex and the respective control. Body weights of the males and females fed 6,000 ppm diet were significantly lower than the respective control. Incidences of hepatocellular carcinomas and hepatocellular adenomas in the females fed diets containing biphenyl were significantly increased in a dose-related manner, and exceeded a range of the historical control data in the Japan Bioassay Research Center. Incidences of basophilic cell foci in the liver were increased in the females fed 2,000 and 6,000 ppm diets. There was no increase in tumor or tumor-related lesion in the males fed diets containing biphenyl. Chronic toxicity of biphenyl was characterized by increased incidences of urothelial desquamation in the renal pelvis in males and females and mineralization in the inner stripe of renal outer medulla in females, as well as changes in serum levels of BUN, ALP and some electrolytes in males and females. In conclusion, the 2-year oral administration of biphenyl-containing diets induced pre-neoplastic and neoplastic lesions in the liver of females and non-neoplastic lesions in the kidney of males and females. Causative factors for the biphenyl-induced hepatocarcinogenicity were discussed in light of our published finding of peroxisome proliferation.     

The comparison of the collagen fiber contents and hepatic stellate cell distribution in male and female chicken livers

The difference in collagen fiber content, morphological properties and hepatic stellate cell (HSC) distribution was investigated in the liver of both sexes in chicken. Collagen fiber specimens were obtained by maceration treatment with NaOH solution. HSCs were detected using desmin‐specific immunohistochemistry. The ratio of liver weight to body weight was larger in the female than the male chickens. Collagen fiber content, the numerical density of HSCs and the percentage area displaying desmin immunopositivity were not different between the right and left lobes of the liver, in both male and female chickens. However, all of these parameters were larger in the males than the females. In the light microscopic observation, many HSCs in the male had large and elongated cytoplasmic processes. Conversely, HSCs with poorly developed cytoplasmic processes were frequently observed in females. Liver tissue is structurally stronger in male chickens than females and the activity and density of HSCs may be related to the collagen fiber content in chicken liver.     

Background data of 2-year-old male and female F344 gpt delta rats

Although gpt delta rats, as reporter gene-transgenic rats, were originally developed for in vivo mutation assays, they have also been used to evaluate chemical carcinogenesis and comprehensive toxicity. Therefore, it is necessary to accumulate background data on carcinogenicity and general toxicity in gpt delta rats. Here, we investigated the background data of 110-week-old male and female F344 gpt delta rats and wild-type rats. There was no effect of reporter gene transfection on animal survival rates and body weights during the experiment. The relative weight of male gpt delta rat adrenals was significantly higher than that of wild-type rats, possibly due to the higher incidence of pheochromocytoma. There were no intergenotype differences in the incidence of nonneoplastic lesions in both sexes, including chronic progressive nephropathy and focus of cellular alteration in the liver, which had a higher incidence in both genotypes. Additionally, the significantly higher incidence of adrenal pheochromocytoma in male gpt delta rats than that in wild-type rats was likely incidental because of the lack of differences in the incidences of preneoplastic (male and female) and neoplastic (female) adrenal lesions in both genotypes. Other neoplastic lesions in both sexes showed no intergenotype differences in incidence rates, although large granular lymphocytic leukemia in the spleen and Leydig cell tumors in the testes of males showed higher incidence rates. Overall, there were no effects of reporter gene transfection on the spectrum of spontaneous lesions in F344 gpt delta rats, thus supporting their applicability in evaluating chemical toxicity and carcinogenicity.     

构树叶饲喂小白鼠引起的性别差异

为研究日本光叶楮及发酵构树叶在动物饲喂上的特点,将72只小白鼠雌雄各半,均分为6组,分别采用日本光叶楮、野生构树的未发酵树叶粉以及发酵构树叶取代等量基础日粮,进行49 d饲养试验。结果表明:光叶楮组料肉比大部分低于野生品种及对照组。发酵组料肉比大部分高于对照组,且随着浓度增加,料肉比先增加后降低。雌性小白鼠在10%构树叶配比(包括光叶楮树叶、野生构树叶以及发酵构树叶)下,第3周起与对照组的体重无显著差异;而雄性小白鼠在试验期内,未发酵构树叶与30%发酵构树叶饲喂对雄性小白鼠的生长影响较明显,未发酵的构树叶饲喂对雄性小白鼠生长的影响相对于雌性来说更显著。适量比例的发酵构树叶(20%)可以促进睾丸增大。30%及以下构树叶配比的饲料对雌雄小白鼠的肝功能均无明显损伤。构树叶毒性对雄性小白鼠影响更大。     

Localization of connexin 32 in spontaneous liver lesions of mice

We examined the localization of connexin 32 (Cx32), a component of gap junctions, in 24-month-old male B6C3F1 mice with spontaneously occurring hepatocellular altered foci or tumors. Immunohistochemically, Cx32-staining intensity in cell-to-cell membranes of altered hepatocytes was decreased in eosinophilic foci and increased in basophilic foci as compared to those in intact hepatocytes. These alterations were enhanced in adenomas and carcinomas with both eosinophilic and basophilic cytoplasm. In cell membranes facing on the sinusoidal portions, the intensities increased in all lesions. Image analyses confirmed that the spot areas of Cx32 were decreased in eosinophilic foci, but increased in basophilic foci, adenomas and carcinomas. These results demonstrate that Cx32 shows different expression in different types of hepatic lesions.     

Effect of fasting duration on clinical pathology results in Wistar rats

Background: Fasting is an important preanalytical factor that may affect the interpretation of hematology and clinical biochemistry data in toxicology or pharmacology studies. Limited information is available on how the results may be affected by different durations of fasting. Objective: The purpose of this study was to assess the influence of fasting duration on clinical pathology results in male and female rats and to determine an optimum fasting time for preclinical studies. Methods: Male and female Wistar rats (10 each per group) were fasted for 0, 4, 8, 16, 24, and 48 hours. Changes in body weight and in the results of routine CBC and clinical chemistry analysis were evaluated by 1‐way ANOVA. Results: Body weight was significantly decreased by 4 hours of fasting in all rats, and hemoglobin concentration was significantly increased at 16 hours in male rats. Serum glucose and triglyceride concentrations in both sexes and cholesterol and high‐density lipoprotein‐C concentrations in female rats were also significantly decreased beginning at 16 hours. The creatinine concentration was increased in females after 16 hours of fasting. Serum alkaline phosphatase and alanine aminotransferase activities were significantly decreased after 8 hours in males and 16 hours in females. Conclusions: Fasting‐induced changes in clinical pathology results were consistent with hemoconcentration and altered nutrition and metabolic function. Most changes occurred at 16 hours, with minimal subsequent changes. Hence, a 16‐hour fasting duration may be recommended for preclinical studies involving clinical pathology measurements.     

Biology of the Rice Rat (Oryzomys palustris natator) in a Laboratory Environment

The pattern of body growth ranging from weaning to old age has been examined by means of parameters of weight and head-body length from 370 rice rats. The differences between the sexes were found to emerge after 20 days until clear demarkation existed in both weight and length by 30 days. Weight was found to have a greater rate of increase relative to length. The males were found to continue to increase weight until 20 months old while length had ceased by 16 months. The females were found to increase weight and length until 14 and 12 months respectively. Since the onset of maturity, both sexual and in body, begins earlier in the female than the male, the cessation of such processes would occur earlier and later respectively. These growth periods occupy the earlier months and are regarded as representatives of growth in length whereas the later increases cannot be placed in the same category.     

Iron content of rat serum ferritin.

The serum ferritin concentration was significantly higher in female than in male rats, reflecting higher iron stores in females than in males. The mean iron/protein ratio of serum ferritin was 0.018+/-0.008 (SD) (microg of Fe/microg of protein) in female rats and 0.011+/-0.011 in male rats, being much lower than that of liver ferritin (0.233+/-0.014 in females and 0.227+/-0.020 in males). Iron loading of rats significantly increased serum ferritin concentration, but did not influence the iron content of serum ferritin. These results indicate that rat serum ferritin contains only a small amount of iron independent of body iron stores.     

Mononuclear cell leukemia in aged Sprague-Dawley rats

A mononuclear cell leukemia in Sprague-Dawley rats is described in which liver, spleen, and lung involvement was a constant feature. The cell was 16 to 25 microns in diameter with round, oval or indented nucleus, and the cytoplasm contained bright red granules. This is the first report of such a leukemia in Sprague-Dawley rats and a comparison with mononuclear cell leukemia in other strains of laboratory rats is made.     

Sexual dimorphism of the normal rat mammary gland.

Sexual dimorphism is a routinely encountered but previously unreported feature of the normal rat mammary gland. Forty male and 40 female F344 rats, 19 weeks of age, were examined retrospectively to document histologic differences that are very apparent when mammary glands of males and females of the same age are compared. Development of the mammary gland starts in utero, and there is reported to be little morphologic difference between males and females at birth. By 19 weeks of age, however, the differences are very noticeable. The mammary glands of females, comprised of scattered tubular ducts and alveolar structures that have distinct lumina lined, usually, by a single layer of cuboidal epithelium, are characterized as tubuloalveolar. In young males, mammary tissue is generally more florid than in females of the same age. There are, scattered within the hypodermis, larger, more contiguous, lobular groups of cells that are distinct for their lack of obvious tubular or ductal orientation. The cells, arranged into alveoli, are generally characterized by abundant, foamy, eosinophilic cytoplasm containing distinct, variably-sized vacuoles. Alveolar lumina are mostly indistinct but may contain evidence of secretory activity. To emphasize the importance of this difference, selected results of a routine toxicity study are discussed in which the mammary glands of male rats, exposed for 52 weeks to cis-N-(1-benzyl-2-methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4- methyl-aminobenzamide, a reported dopamine antagonist, underwent distinctive histomorphologic changes. As a result of exposure to this compound, the lobuloalveolar structure described as normal for male rats assumed characteristics of a tubuloalveolar morphology indistinguishable from that seen in the unexposed females.(ABSTRACT TRUNCATED AT 250 WORDS)     

étude Histomorphométrique des Variations Morphologiques du Follicule Thyroïdien chez le Rat en Fonction de l''âge et du Sexe

The thyroid glands of male and female rats (Sprague Dawley) 10 to 60 weeks of age were examined histomorphometrically. The results show a clear sex dimorphism. The thyroid follicles in the male animals show a greater functional activity than in the female animals. But while the morphology of the follicles in the females was constant throughout the period of observation, in the males the activity gradually diminished.     

No significant differences were observed in the amounts of DNA strand breaks produced by copper between male and female liver cells of long-evans cinnamon (LEC) strain rats.

The amounts of DNA single strand breaks that are oxidative damage produced by copper were examined by comet assay in the liver cells of an inbred strain of Long-Evans Cinnamon (LEC) rats that spontaneously develops fulminant hepatitis. At 4 weeks of age, copper contents in the liver of LEC rats were approximately 30-fold higher than those of WKAH rats that are control rats used in the present study. Copper accumulated in the liver of LEC rats in an age-dependent manner and no significant differences were observed between copper contents in the livers of males and females at each week of age from 4 to 15 weeks. No significant amounts of DNA strand breaks were found in the liver cells of both male and female WKAH rats from 4 to 15 weeks of age. DNA strand breaks were produced in the substantial population of LEC rat liver cells at 10 weeks of age and induced in an age-dependent manner from 10 to 15 weeks of age. The amounts of DNA strand breaks produced by copper accumulation in the liver cells of female LEC rats are not more abundant than those in the cells of male rats, although it has been reported that hepatitis in female rats is more serious than that in male rats.     

Size Allometry in Mink (Mustela vison) Selected for Feed Efficiency

Objectives were to analyse absolute and relative size of mink at maturity, and to test effects of selection line, sex and interaction on size. For male and female mink selected for high or low feed efficiency, size at 30 weeks was analyzed for body weight, carcass weight, pelt weight, subcutaneous fat weight, and pelt length. For absolute size, an ANOVA model included effects of line, sex, and interaction. For relative size, two models were used: an allometric model and an extended allometric model, which included effects of line, sex, and interaction.

For the ANOVA model, sexes differed for each variable; females were less than males. As a percentage of body weight, however, carcass weight was larger in females than males, whereas fat weight was smaller in females than males. For the extended allometric growth model, sexes differed for carcass weight and subcutaneous fat weight; females fattened faster than males.