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1.
Neither analysis of the urinary catecholamine metabolites vanillymandelic acid and 4-hydroxy-3-methoxyphenylglycol nor blood pressure measurements allowed the detection of adrenal medullary tumors or hyperplasia in 115 aged male Wistar rats (70 rats, 24 months of age and 45 rats, 30 months of age). Histochemical examination of the adrenal glands demonstrated that the 55 hyperplastic and 25 neoplastic lesions of the medulla usually had little or no chromaffinity. Chromaffinity was found comparable to normal medulla in only three tumors examined histochemically. Of these tumors, two were partially and one completely chromaffin-positive, but all three were small and did not result in elevated blood pressure or catecholamine metabolite excretion values. These observations indicate that excessive catecholamine synthesis and release is not a feature of adrenomedullary tumors and hyperplasia occurring spontaneously in aged male Wistar rats.  相似文献   

2.
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.  相似文献   

3.
Spontaneous renal tubule tumors (RTTs), with a distinctive morphological phenotype, were present in three Sprague-Dawley rats, 1 male and 2 females, out a total of 120 animals of each sex from untreated and placebo control groups in a 2-year carcinogenicity study. One female had one carcinoma, adenoma and hyperplasia, and the other female had five adenomas and many hyperplastic lesions; the male case had one carcinoma. From these cases, a biological continuum of hyperplasia, adenoma and carcinoma could be recognized. The tumors were present in the renal cortex and appeared as solid lobulated growths with occasional central necrosis. The lobules were divided by a small amount of fibrovascular tissue. Occasionally the larger tumors contained a cystic area. Tumor cells appeared distinctive and exhibited variable amounts of eosinophilic/amphophilic and vacuolated cytoplasm. Nuclei were round to oval with a prominent nucleolus. Mitotic figures were uncommon, and no distant metastasis was noted. The tumors were seen as multiple and bilateral lesions in two animals and had no apparent relationship to chronic progressive nephropathy (CPN). Foci of tubule hyperplasia were also noted to contain the same type of cellular morphology. The morphological and biological features of these 3 cases resembled the amphophilic-vacuolar (AV) variant of RTT that has been posited to be of familial origin. This is a report of spontaneous familial renal tumors in Sprague-Dawley rats from Japan.  相似文献   

4.
Tapeworm cysts were identified in liver of Wistar rats and it induced fibrosarcoma in liver and gastroenteropathy in stomach and intestine. The tapeworm larva was confirmed as Strobilocercus fasciolaris by PCR linked mitochondrial DNA sequencing. Light microscopy, special staining (masson trichrome) and immunoflouresence supported the diagnosis of fibrosarcoma. Infiltration of plasma cells, macrophages and eosinophils were observed in the liver section. Gastric mucosal hyperplasia, dilation of gastric glands with secretion, intestinal mucosal cell hyperplasia, proliferation of duodenal submucosal glands were confirmed by light microscopy and supported by PAS, AB staining. The concomitant development of hepatic sarcoma and gastroenteropathy by larvae of Taenia taeniaeformis (S. fasciolaris) infection is very rare and is the first reported case in Wistar rats to our knowledge.  相似文献   

5.
Naturally occurring aflatoxicosis is described in goats fed a concentrate mixture containing polkudu meal (defatted residue from grated coconut after juice extraction). Toxigenic strains of Aspergillus flavus were present in the concentrate and aflatoxins were recovered from the liver and urine of affected animals. Hepatic lesions in poisoned goats consisted of bile duct hyperplasia and periportal fibrosis; renal lesions included necrosis of tubular epithelial cells and proteinaceous exudation in the glomerular space. Similar lesions were produced experimentally in goats with aflatoxin and the coconut cultures of A flavus. High doses of aflatoxin B1 produced, in addition, hepatic centrilobular congestion, haemorrhage and periportal fatty change.  相似文献   

6.
The effect of dimethoate at two dosage levels (6.25 and 12.50 mg/kg b. wt.) on male reproduction tissues and their tissue residues in rats were studied. The tested doses were given orally to male rats for 65 consecutive days. Sex organs weight analysis, semen picture, testosterone levels and histopathology of the male genital organs were the criteria used to evaluate the reproductive efficiency of the treated rats. There was a dose-related decrease in the weights of most genital organs and sperm motility associated with an increase in the percentages of dead and morphologically abnormal spermatozoa of treated rats. A decrease in plasma testosterone levels was observed in the treated groups. Histological examination revealed that dimethoate caused testicular lesions characterized by moderate to severe degenerative changes of spermatogonial cells and by partial arrest of spermatogenesis. Sections from liver revealed that the central veins and hepatic sinusoids appeared dilated, with some areas of haemorrhage. The highest concentrations from dimethoate were found in liver and tests and the lowest in skeletal muscle. Dimethoate and its metabolite analog were still present in a detectable concentration 21 days after stopping its oral administration.  相似文献   

7.
Pathogenesis of tularemia in nonimmune rats given (intraperitoneal inoculation) virulent strain (SCHU S4) or vaccinal strain (LVS) of Francisella tularensis and in immune rats given SCHU S4 is described. Both LVS and SCHU S4 caused pyogranulomas in liver and spleen of nonimmune rats. Nonimmune rats given 10(4) SCHU S4 organisms did not survive beyond 72 hours, but immune rats given challenge inoculum of 10(8) SCHU S4 organisms developed lesions and survived. Larger doses of LVS resulted in earlier onset of characteristic hepatitis and splenitis in nonimmune rats. Periportal lymphocytic infiltrates were present in the liver 48 hours after SCHU S4 challenge inoculation of immune rats and 96 hours after inoculation of LVS in nonimmune rats and were associated with intense macrophage aggregation. These changes indicate that the pathogenesis of tularemia is a result of the interdependency of the dose and virulence of the causative agent with the immune status of the host and that cellular immunity has a significant role in the response of the rat to tularemia.  相似文献   

8.
The WHO International Programme on Chemical Safety (IPCS) framework for analyzing the relevance of a cancer mode of action (MoA) for humans (IPCS cancer-HRF) is an application to assess human relevance of tumorigenic hazards found through rodent bioassays. The chloroacetanilide herbicides, butachlor and alachlor, induced enterochromaffin-like (ECL) cell tumors in rat stomachs, at the highest doses. This study analyzed the human relevance of this tumor by applying the IPCS cancer-HRF using published data. In a postulated MoA, early key events (KEs) included decreased mucosal thickness in the fundic region, due to reduced parietal cells. The following KEs included increased pH of gastric acid and hypergastrinemia, leading to enhanced cell proliferation and hyperplasia, and resulting in the outcome of an ECL cell tumor. The data showed consistencies in dose-response and temporal concordance with the KEs and specificity in the tumor response, providing strengthened evidence of the KEs. While the early KE was not the same, similar MoAs have already been established for omeprazole and ciprofloxacin. The integrated data indicated that the postulated MoAs were biologically plausible. Alternative MoAs were excluded.. Based on sufficient evidence, an MoA was established in rats. When addressing chemically inducible MoAs of human relevance, KEs of hypergastrinemia and trophic ECL cell hyperplasia were judged to not be qualitatively and quantitatively plausible in humans. The MoA in rats is unlikely to be present in humans; however, the potential effects on parietal cells cannot be excluded. Thus, the IPCS cancer-HRF is very useful for assessing human relevance.  相似文献   

9.
It is extremely rare to have multiple spontaneous proliferative lesions in young adult rats. Here, we report the occurrence of different proliferative lesions in multiple tissues of a 7-week-old female rat in a 1-week repeated toxicity study. Grossly, multiple white patches and nodules in the bilateral kidneys, femoral and subcutaneous masses, and a nodule in the liver were observed. Renal lesions were diagnosed as renal mesenchymal tumors. One of the femoral subcutaneous masses was diagnosed as an adenolipoma consisting of mammary epithelial cells and mature adipocytes. The other femoral and abdominal subcutaneous masses were diagnosed as lipomas consisting of mature adipocytes. The liver nodule was diagnosed as non-regenerative hepatocellular hyperplasia, which was characterized by the proliferation of slightly hypertrophic hepatocytes. In the cauda equina, the growth of enlarged Schwann cells around the axon was observed, and this lesion was diagnosed as a neuroma.  相似文献   

10.
A polybrominated biphenyl fire retardant (Firemaster FF-1) was responsible for the widespread environmental contamination and animal losses in Michigan during 1973 and 1974. In Fischer 344/N rats orally given 30,100,300, and 1,000 mg/kg (5 days/week, 22 total doses) for 4.5 weeks and observed for 90 days after the start of treatment, the LD50 was determined to be 65 mg/kg/day (total 1.43 g/kg) for the female rat and 149 mg/kg/day (total 3.28 g/kg) for the male. All female rats given the dosage of 100 mg/kg/day (22 doses, total 2.20 g/kg) died between 41 and 53 days after the start of treatment, whereas 38% of the males died between 50 and 73 days. Pathologic changes in treated rats were large liver, accentuation of the hepatic lobular markings, and atrophy of thymus and spleen. Microscopically, hepatic changes were characterized by congestion, fatty metamorphosis, and multifocal liquefactive necrosis. Male rats given 100 mg/kg/day and dying after 90 days had subacute to chronic hepatitis with marked focal proliferation of bile ducts. Exposure to Firemaster FF-1 may produce atypical liver nodules in the rat as early as 6 months after they were first given the preparation. Marked hepatotoxic effect persisted in surviving rats when examined after 6 months.  相似文献   

11.
A syndrome of male pseudohermaphroditism, cryptorchidism, and testicular neoplasia was diagnosed in 3 Miniature Schnauzers. The dogs had clinical signs of hyperestrogenism and were either unilateral or bilateral cryptorchids. At surgery, it was discovered that the dogs were male pseudohermaphrodites, having intra-abdominal testes containing Sertoli cell tumors and uteri that had undergone endometrial cystic hyperplasia.  相似文献   

12.
The purposes of the present study were to evaluate the hepatocarcinogenicity of concurrent treatment of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and diethylnitrosamine (DEN) in rats and to determine whether no effect levels of combinations of these two different structural categories of genotoxic hepatocarcinogens exist. Two 16-week rat hepatocarcinogenesis assays were performed using a total of 790 male F344 rats. In experiment 1, we evaluated the effects of concurrent treatment of a subcarcinogenic dose of DEN on rat hepatocarcinogenesis induced by various doses of MeIQx. In experiment 2, we determined hepatocarcinogenicities of combinations of MeIQx and DEN at subcarcinogenic doses, low carcinogenic doses and high carcinogenic doses. Quantitative analyses of glutathione S-transferase placental form (GST-P)-positive foci, a preneoplastic lesion of the liver in rats, revealed that concurrent treatment with subcarcinogenic doses of DEN did not enhance MeIQx-induced rat hepatocarcinogenicity. We also found that concurrent treatment with combinations of subcarcinogenic doses of DEN and MeIQx was not hepatocarcinogenic, indicating that the combined effects of subcarcinogenic doses of DEN and MeIQx were neither additive nor synergistic. Moreover, concurrent treatment with low carcinogenic doses of these 2 carcinogens did not show additive or synergistic effects. Synergetic effects were observed only in rats coadministered high carcinogenic doses of the 2 carcinogens. These results demonstrate the existence of no effect levels of combinations of these 2 genotoxic hepatocarcinogens, and provide new evidence supporting our idea that there is a threshold, at least a practical threshold, that should be considered when evaluating the risk of genotoxic carcinogens.  相似文献   

13.
Six- to eight-week-old gnotobiotic F344/N rats were inoculated intranasally with 10(5.0) colony-forming units of Mycoplasma pulmonis or were sham inoculated, then one week later were given 10(0.2) 50% tissue culture infective doses of Sendai virus or sterile medium. Groups of rats were killed immediately after virus inoculation and three, five, ten, and 20 days later. Lesions in nasal passages, middle ears, larynxes, tracheas, and lungs from half of the rats in each group were subjectively scored. Organs from the other rats were quantitatively cultured for M. pulmonis and for Sendai virus. Rats given Sendai virus alone had mild, patchy, necrotizing rhinitis, laryngitis, tracheitis, and bronchitis, but not bronchiolitis or interstitial pneumonia. M. pulmonis alone induced mild lesions of murine respiratory mycoplasmosis including mild to moderate suppurative rhinitis, otitis media, laryngitis, and tracheitis with submucosal lymphoid accumulation and epithelial hyperplasia, but not lung lesions. Rats given M. pulmonis and Sendai virus had severe lesions characteristic of advanced mycoplasmal disease throughout the respiratory tract, including suppurative bronchitis with extensive lymphoid accumulations and epithelial hyperplasia; some rats also had suppurative pneumonia and bronchiectasis. Larger numbers of M. pulmonis colony-forming units were in rats given Sendai virus, but there was no statistically significant difference in Sendai virus infectious units between rats also given M. pulmonis and those given virus only.  相似文献   

14.
Little information is available on the relationship between computed tomography (CT) imaging findings and the pathologic diagnosis of canine hepatic tumors. Our purpose was to clarify the characteristic features of CT findings in liver tumors in dogs. Data from 33 dogs with either a hepatocellular carcinoma, n = 14, hepatocellular adenoma, n = 14, or nodular hyperplasia, n = 5 were summarized from medical records. CT features for each histologic diagnosis were characterized and analyzed statistically. Common findings in hepatocellular carcinoma included central (79%, P = 0.0030) and marginal enhancement (93%, P = 0.00043) in the arterial phase, cyst-like lesions (93%), capsule formation (93%), and hypoattenuation in the portal (86%), and equilibrium phases (93%). Hepatic adenoma was characterized by a characteristic diffuse enhancement pattern during the arterial phase (57%, P = 0.013), which was also found in nodular hyperplasia (60%), but never in hepatocellular carcinoma. Nodular hyperplasia was less likely to have a capsule structure (20%, P = 0.0087). Mass size was significantly smaller in nodular hyperplasia than in hepatocellular carcinoma and hepatic adenoma (P = 0.0033 and 0.038, respectively). Hyperattenuation in the arterial and the portal phase i.e. contrast retention, was more frequent in hepatic adenoma than in the other groups (P = 0.037 and 0.037, respectively). Nodular hyperplasia was more frequently isoattenuating in the equilibrium phase (P = 0.043).  相似文献   

15.
This report describes the antemortem diagnosis and antemortem and postmortem findings of superficial necrolytic dermatitis with hepatopathy (i.e., hepatocutaneous syndrome) in a cat. A 5-year-old Maine coon was evaluated because of a history of pruritic alopecia and liver enzyme elevations. Abdominal ultrasonography revealed a reticular pattern to the hepatic parenchyma. Histopathological findings of the liver were nodular regeneration with bands of vacuolated hepatocytes and bile duct hyperplasia, characteristic of the hepatopathy frequently associated with superficial necrolytic dermatitis. Skin histopathology revealed multifocal parakeratosis, midepidermal spongiosis, and basal cell hyperplasia consistent with superficial necrolytic dermatitis.  相似文献   

16.
A lead salt mixture was given orally to nine dogs at 5–10 mg/kg/day for periods varying from 14 to 152 days. Macroscopic lesions included reddening of bone marrow and gastric ulceration. Jaundice occurred in dogs receiving high total lead dosage. Histopathologically, periacinar fatty change in the liver was a consistent finding and at high doses of lead, this was accompanied by cholestasis and biliary hyperplasia. Testicular degeneration and aspermia was found in two of the three male dogs. Acid-fast lead inclusions were present in the liver, kidney and osteoclasts.  相似文献   

17.
Long-term studies of megestrol acetate and chlormadinone acetate in 100 female dogs are in progress. Doses of zero, one, 10 and 25 times the expected human dose of megestrol acetate and 25 times the expected human dose of chlormadinone acetate (on a milligram per kilogram body weight basis) are being given daily. During the first 4 years, eight dogs from each of the five groups were killed. The principal gross findings included enlarged uteri with mucoid material in the lumina, mammary development in dogs given middle and high doses of megestrol acetate and chlormadinone acetate, and thickened gallbladder walls in dogs given high doses of each. Histologic evaluation showed inhibition of ovulation for progestogen-treated dogs and suppression of ovarian follicular development with the high doses. Cystic endometrial hyperplasia was slight in the low-dose dogs and moderate to severe in most of the high-dose dogs; a few also had ulcerative endometritis and pyometra. The mammary glands of dogs given the middle and high doses produced lobules, acini, and secretion exceeding natural metestrus. Slight to marked cystic mucinous hyperplasia occurred in the gallbladders of most dogs given the high doses. Tow high-dose megestrol dogs had clinical signs and microscopic pancreatic, renal, and ocular changes indicative of diabetes mellitus.  相似文献   

18.
The effects of feeding varied levels of low- and high-gramine yellow lupin seeds (LG and HG, respectively), and of synthetic gramine added to the diets in amounts ranging from 0.15 to 1.2 g per kg were investigated in one experiment on growing chicken and in two experiments on growing rats. The comparison of LG and HG lupin and the effect of 0.5 g gramine per kg of LG diet were determined in a growth-balance experiment with pigs. Organ weights and histology, blood parameters and activity of liver enzymes were determined. The response to HG lupin and gramine concentration varied among the species, the rats being more affected than chicken; no adverse effects of HG lupin or gramine were found in growing pigs. The common reaction of rats and chicken to the high levels of gramine (native or synthetic) was the decrease of feed intake and body gain. The increase of the relative weight of liver or kidney, changes in hematological parameters and liver enzymes were found only in rats. The estimated NOAEL (no-observed-adverse-effect level) of gramine was about 0.3 g/kg diet for rats, 0.65 g for chicken and at least 0.5 g for growing pigs.  相似文献   

19.
本试验旨在研究地顶孢霉培养物对大鼠生长性能、血清与肝脏抗氧化以及免疫指标的影响。选用体重相近的SD大鼠40只,随机分成5组,每组8个重复,每个重复1只大鼠。5组分别是对照组和4个不同地顶孢霉培养物剂量组(10、50、250和1 250 mg/kg BW组),连续灌胃21 d。结果表明:地顶孢霉培养物极显著提高大鼠的平均日增重(P0.01);提高了大鼠肝脏指数、胸腺指数;提高了大鼠血清中总蛋白(TP)、白蛋白(ALB)、球蛋白(GLB)和葡萄糖(GLU)含量,降低了谷丙转氨酶(ALT)、谷草转氨酶(AST)活力和低密度脂蛋白(LDL)含量;提高了血清和肝脏中谷胱甘肽过氧化物酶(GSH-Px)活力和总抗氧化能力(T-AOC),降低丙二醛(MDA)含量,同时提高了肝脏中的总超氧化物歧化酶(T-SOD)含量;提高了血清免疫球蛋白A、免疫球蛋白G和免疫球蛋白M含量,同时提高血清和肝脏中白介素-4(IL-4)含量,降低白介素-1β(IL-1β)和白介素-17(IL-17)含量。综合各项指标,地顶孢霉培养物能够提高SD大鼠平均日增重,改善血清生化指标,提高大鼠机体抗氧化能力和免疫能力,其中以250 mg/kg BW的添加量为最佳。  相似文献   

20.
Rats and pigs were vaccinated against Trichinella spiralis spiralis either by feeding infective larvae of the subspecies, Trichinella spiralis nativa in musculature or by gavage. The number of larvae established in the musculature of vaccinated nonchallenged and vaccinated challenged rats and pigs were negligible and statistically comparable, while highly significant infections were established in the nonvaccinated challenged rats and pigs. High vaccination doses of T. spiralis nativa gave virtually complete protection to challenge with T. spiralis spiralis in pigs. The results of one trial in rats with a lower vaccination dose of larvae suggest that there is a minimal vaccination dose of larvae required to elicit marked resistance to challenge. The low numbers of muscle larvae established due to the high vaccination doses of larvae confirm the low infectivity of the subspecies, T. spiralis nativa in rats and pigs.  相似文献   

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