Li Y.,Biotoxtech Co. |
Shiraiwa K.,Bioresearch Center Co. |
Ko K.-N.,Biotoxtech Co. |
Moon J.,Biotoxtech Co. |
And 9 more authors.
Experimental and Toxicologic Pathology
A small cardiac tumor was detected in the posterior wall of the left atrium of a 110-week-old female Wistar Hannover rat (Slc: Wistar Hannover/Rcc) during a carcinogenicity historical control study. Tumor was consisted of 2 different cells. Most of the tumor cells were polygonal to oval in shape and had slightly basophilic and granular cytoplasm. These cells were arranged in distinctive cell nests, called 'Zellballen', and were separated by reticulin fibers. The nuclei were round to slightly oval. A few mitotic figures were found. Cytoplasmic granules of tumor cells were negative for Fontana-Masson and Periodic acid Schiff (PAS) staining. Immunohistochemical staining revealed that the chief cells in the tumor were positive for the neuroendocrine markers synaptophysin and chromogranin A but were negative for S-100 protein, vimentin, cytokeratin, α-smooth muscle actin, and calcitonin. In contrast, the surrounding sustentacular cells, other type of tumor cells, were positive for only S-100 protein. The immunohistochemical properties of the tumor cells were quite similar to those of the aortic body. The tumor cells had infiltrated the myocardium of the left atrium and were also noted within vessels. Based on these findings, the tumor was diagnosed as a paraganglioma originating from the aortic body. © 2012 Elsevier GmbH. Source
Itoh M.,Tokyo Medical University |
Tsuji T.,Tokyo Medical University |
Nakamura H.,Tokyo Medical University |
Yamaguchi K.,Tokyo Womens Medical University |
And 4 more authors.
Context: Cigarette smoke (CS) causes both pulmonary and extrapulmonary disorders. Objective: To determine the pulmonary and extrapulmonary effects of acute CS exposure in regard to inflammation, oxidative stress and DNA damage. Materials and methods: Mice were exposed to CS for 10 days and then their lungs, heart, liver, pancreas, kidneys, gastrocnemius muscle and subcutaneous (inguinal and flank) and visceral (retroperitoneum and periuterus) adipose tissues were excised. Bronchoalveolar lavage fluid samples were obtained for differential cell analysis. Inflammatory cell infiltration of the tissues was assessed by immunohistochemistry for Mac-3+ cells, F4/80+ cells and CD45+ cells. Oxidative stress was determined by immunohistochemistry for thymidine glycol (a marker of DNA peroxidation) and 4-hydroxy hexenal (a marker of lipid peroxidation), by enzyme-linked immunosorbent assay for protein carbonyls (a marker of protein peroxidation) and by measurements of enzyme activities of glutathione peroxidase, superoxide dismutase and catalase. DNA double-strand breaks were assessed by immunohistochemistry for γH2AX. Results: CS exposure-induced inflammatory cell infiltration, oxidative stress and DNA damage in the lung. Neither inflammatory cell infiltration nor DNA damage was observed in any extrapulmonary organs. However, oxidative stress was increased in the heart and inguinal adipose tissue. Discussions: Induction of inflammatory cell infiltration and DNA damage by acute CS exposure was confined to the lung. However, an increased oxidative burden occurred in the heart and some adipose tissue, as well as in the lung. Conclusions: Although extrapulmonary effects of CS are relatively modest compared with the pulmonary effects, some extrapulmonary organs are vulnerable to CS-induced oxidative stress. © 2014 Informa Healthcare USA, Inc. All rights reserved. Source
Nakane F.,Bioresearch Center Co. |
Kunieda M.,Bioresearch Center Co. |
Shimiz S.,Bioresearch Center Co. |
Kobayashi Y.,Bioresearch Center Co. |
And 6 more authors.
Journal of Toxicological Sciences
The 26-week oral toxicity of diheptyl phthalate (DHP), a peroxisome proliferator-activated receptor α (PPARα) agonist, with special emphasis on the potential induction of hepatocellular proliferative lesions was investigated in this study. DHP was administered to male F344 rats via gavage at 0 (control), 1,000 or 2,000 mg/kg/day for 26 weeks. Body weight gain was significantly lower, whereas food and water consumption was significantly higher in DHP-treated rats compared with controls. DHPtreated rats exhibited decreases in blood triglyceride, total cholesterol, phospholipid and glucose levels, which were likely related to biological effects of the PPARα agonist. Absolute and relative organ weights of the livers with pale brown discoloration and dark brown spots significantly increased in DHP-treated rats. Histopathological examinations revealed remarkable diffuse hypertrophy of hepatocytes with groundglass appearance, intracytoplasmic inclusion bodies and/or vacuolation in the DHP-treated groups. These findings were associated with increases in serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and γ-glutamyltranspeptidase. The number and area of glutathione S-transferase placental form positive foci, a marker of hepatocellular preneoplastic lesions in rats, significantly increased in DHP-treated groups. Additionally, proliferating cell nuclear antigen positive liver cell counts in DHPtreated groups were significantly higher than those of the controls. Testicular alterations were not detected histopathologically, whereas absolute and relative prostate weights significantly decreased at both doses. These results indicate that DHP induces liver pre-neoplastic foci, and suggest the possibility that DHP is a possible genotoxic carcinogen in the liver of rats. Source