Journal of Toxicologic Pathology最新文献

{"title":"A carcinogenicity study of diphenylarsinic acid in C57BL/6J mice in drinking water for 78 weeks.","authors":"Takashi Yamaguchi,&nbsp;Min Gi,&nbsp;Masaki Fujioka,&nbsp;Shugo Suzuki,&nbsp;Yuji Oishi,&nbsp;Hideki Wanibuchi","doi":"10.1293/tox.2022-0111","DOIUrl":"https://doi.org/10.1293/tox.2022-0111","url":null,"abstract":"<p><p>Diphenylarsinic acid (DPAA), a neurotoxic organic arsenical, is present in groundwater and soil in some regions of Japan owing to illegal dumping. The present study evaluated the potential carcinogenicity of DPAA, including investigating whether bile duct hyperplasia in the liver that was observed in a chronic study on 52 week mouse, develops into a tumor when administered to mice in their drinking water for 78 weeks. DPAA was administered to 4 groups of male and female C57BL/6J mice at concentrations of 0, 6.25, 12.5, and 25 ppm in drinking water for 78 weeks. A significant decrease in the survival rate was found for females in the 25 ppm DPAA group. Body weights of males in the 25 ppm and females in the 12.5 and 25 ppm DPAA groups were significantly lower than those of the controls. Histopathological evaluation of neoplasms in all tissues showed no significant increase in tumor incidence in any organ or tissue of 6.25, 12.5, or 25 ppm DPAA-treated male or female mice. In conclusion, the present study demonstrated that DPAA is not carcinogenic to male or female C57BL/6J mice. Taken together with the fact that the toxic effect of DPAA is predominantly restricted to the central nervous system in humans, and the finding that DPAA was not carcinogenic in a previous 104-week rat carcinogenicity study, our results suggest that DPAA is unlikely to be carcinogenic in humans.</p>","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"36 2","pages":"123-129"},"PeriodicalIF":1.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8e/bb/tox-36-123.PMC10123301.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9726285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contribution of toxicological pathology to occupational health: lung carcinogenicity of fibrous and particulate substances in rats.","authors":"Shoji Fukushima,&nbsp;Tatsuya Kasai,&nbsp;Hideki Senoh,&nbsp;Yumi Umeda,&nbsp;Takashi Mine,&nbsp;Toshiaki Sasaki,&nbsp;Hitomi Kondo,&nbsp;Michiharu Matsumoto,&nbsp;Shigetoshi Aiso","doi":"10.1293/tox.2022-0086","DOIUrl":"https://doi.org/10.1293/tox.2022-0086","url":null,"abstract":"<p><p>In this review, we focus on the rat pulmonary carcinogenicity of two solid substances, fibrous multi-walled carbon nanotube (MWCNT) and particulate indium tin oxide (ITO). Inhalation exposure to MWNT-7, a type of MWCNTs, and ITO induced lung carcinogenicity in both male and female rats. Toxicity to the alveolar epithelium is induced by macrophages undergoing frustrated phagocytosis or frustrated degradation of engulfed particles (referred to as frustrated macrophages). Melted macrophage contents contribute significantly to development of hyperplasia of the alveolar epithelium, which eventually results in the induction of lung carcinoma. MWNT-7 and ITO induce secondary genotoxicity; consequently, a no-observed-adverse-effect level can be applied to these materials rather than benchmark doses that are used for non-threshold carcinogens. Thus, establishing occupational exposure limit values for MWNT-7 and ITO based on the existence of a carcinogenic threshold is reasonable.</p>","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"36 2","pages":"69-83"},"PeriodicalIF":1.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d7/f4/tox-36-069.PMC10123297.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9357309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative analysis of neurofilament light chain levels in the serum and cerebrospinal fluid in rats subjected to partial sciatic nerve ligation.","authors":"Tomoya Sano,&nbsp;Yasushi Masuda,&nbsp;Hironobu Yasuno,&nbsp;Takeshi Watanabe,&nbsp;Tadahiro Shinozawa","doi":"10.1293/tox.2022-0110","DOIUrl":"https://doi.org/10.1293/tox.2022-0110","url":null,"abstract":"<p><p>Neurofilament light chain (NfL) has recently been used as a biomarker of neurodegeneration. Although cerebrospinal fluid (CSF) NfL levels are hypothesized to affect blood NfL levels, whether blood NfL levels change independently of the CSF during peripheral nerve injury remains unclear. Thus, we evaluated the nervous tissues histopathology and serum and CSF NfL levels in partial sciatic nerve-ligated rats at 6 h and one, three, or seven days after the surgery. Sciatic and tibial nerve fiber damage was observed at 6 h after the surgery, and peaked at three days postoperatively. The serum NfL levels peaked 6 h to one day after ligation, but they tended to return to the normal seven days after ligation. However, the CSF NfL levels were unchanged throughout the study period. In conclusion, the comparative evaluation of serum and CSF NfL levels can provide useful information as biomarkers of nerve tissue damage and its distribution.</p>","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"36 2","pages":"145-149"},"PeriodicalIF":1.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fc/5a/tox-36-145.PMC10123296.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9356503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ectopic pancreatic acinar cell carcinoma in the thoracic cavity of F344 rat.","authors":"Chinatsu Fujiwara,&nbsp;Shinya Miyazaki,&nbsp;Yoshitaka Katoh,&nbsp;Tsuyoshi Ito,&nbsp;Aya Koyama,&nbsp;Naofumi Takahashi,&nbsp;Atsushi Shiga,&nbsp;Takanori Harada","doi":"10.1293/tox.2022-0114","DOIUrl":"https://doi.org/10.1293/tox.2022-0114","url":null,"abstract":"<p><p>Ectopic pancreatic tissue can occasionally cause inflammation, hemorrhage, stenosis, and invagination, similar to normal pancreatic tissue; however, tumorigenesis is rare. This case report describes an ectopically observed pancreatic acinar cell carcinoma in the thoracic cavity of a female Fischer (F344/DuCrlCrlj) rat. Histopathologically, polygonal tumor cells with periodic acid-Schiff-positive cytoplasmic eosinophilic granules showed solid proliferation and infrequently formed acinus-like structures. Immunohistochemically, the tumor cells were positive for cytokeratin, trypsin, and human B-cell leukemia/lymphoma 10, which specifically reacted with pancreatic acinar cells, and negative for vimentin and human α-smooth muscle actin. Ectopic pancreas develops in the submucosa of the gastrointestinal tract; however, there are few reports of its development and neoplasia in the thoracic cavity. To the best of our knowledge, this is the first report of ectopic pancreatic acinar cell carcinoma in the thoracic cavity of a rat.</p>","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"36 2","pages":"139-143"},"PeriodicalIF":1.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e8/f3/tox-36-139.PMC10123294.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9357302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A mammary fibroadenoma with terminal end buds-like structures in a 7-week-old male SD rat.","authors":"Yumiko Kamiya,&nbsp;Tsubasa Saito,&nbsp;Moeko Aoki,&nbsp;Mizuho Takagi,&nbsp;Kochi Kakimoto,&nbsp;Yuko Yamaguchi","doi":"10.1293/tox.2022-0071","DOIUrl":"https://doi.org/10.1293/tox.2022-0071","url":null,"abstract":"<p><p>We report a case of mammary fibroadenoma in a 7-week-old male SD rat. This case showed rapid growth within one week from the time when the nodule was detected. Histologically, the nodule was a well-circumscribed subcutaneous mass. The tumor consisted of an epithelial component with island-like proliferation (cribriform to tubular patterns) and an abundant mesenchymal component. Alpha-SMA-positive cells were arranged at the periphery of the epithelial component and showed cribriform and tubular patterns. Discontinuous basement membranes and high cell proliferative activities were observed in the cribriform area. These features resembled those of normal terminal end buds (TEBs). Since the mesenchymal component had abundant fine fibers and a mucinous matrix, its stroma was regarded as neoplastic growth of fibroblasts; thus, this tumor was diagnosed as a fibroadenoma. This case is an extremely rare fibroadenoma in that it occurred in a young male SD rat and was composed of an epithelial component showing multifocal proliferation of TEB-like structures and a mucinous mesenchymal component consisting of fibroblasts with fine collagen fibers.</p>","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"36 2","pages":"131-138"},"PeriodicalIF":1.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/aa/3f/tox-36-131.PMC10123299.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9357300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophage pathology in hepatotoxicity.","authors":"Jyoji Yamate, Takeshi Izawa, Mitsuru Kuwamura","doi":"10.1293/tox.2022-0112","DOIUrl":"10.1293/tox.2022-0112","url":null,"abstract":"<p><p>The liver is the most important organ that metabolizes and detoxifies chemicals taken into the body. Therefore, there is always a risk of liver damage owing to the toxic effects of chemicals. The mechanisms of hepatotoxicity have been studied extensively and deeply based on toxic effects of chemicals themselves. However, it is important to note that liver damage is variously modified by the patho-biological reactions evoked mainly via macrophages. Macrophages appearing in hepatotoxicity are evaluated by the M1/M2 polarization; M1 macrophages promote tissue injury/inflammation, whereas M2 macrophages show anti-inflammatory action including reparative fibrosis. The \"portal vein-liver barrier\" regulated by Kupffer cells and dendritic cells in and around the Glisson's sheath may be related to the initiation of hepatotoxicity. In addition, Kupffer cells exhibit the two-sides of functions (that is, M1 or M2 macrophage-like functions), depending on microenvironmental conditions which may be raised in part by gut microbiota-derived lipopolysaccharide. Furthermore, damage-associated molecular patterns (DAMPs) (in particular, HMGB1) and autophagy (which degrades DAMPs) also play roles in the polarity of M1/M2 macrophages. The mutual relation of \"DAMPs (HMGB-1)-autophagy-M1/M2 macrophage polarization\" as the patho-biological reaction should be taken into consideration in hepatotoxicity evaluation.</p>","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"36 2","pages":"51-68"},"PeriodicalIF":0.9,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/62/1b/tox-36-051.PMC10123298.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9357303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A critical review of the pathogenesis of nasal cavity tumors induced in rodents","authors":"Akiyoshi NISHIKAWA, Kasuke NAGANO, Hajime KOJIMA, Shoji FUKUSHIMA, Kumiko OGAWA","doi":"10.1293/tox.2023-0098","DOIUrl":"https://doi.org/10.1293/tox.2023-0098","url":null,"abstract":"","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"175 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135310650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene expression analysis of antioxidant and DNA methylation on the rat liver after 4-week wood preservative chromated copper arsenate exposure.","authors":"Naofumi Takahashi,&nbsp;Satoru Yamaguchi,&nbsp;Ryouichi Ohtsuka,&nbsp;Makio Takeda,&nbsp;Toshinori Yoshida,&nbsp;Tadashi Kosaka,&nbsp;Takanori Harada","doi":"10.1293/tox.2022-0093","DOIUrl":"https://doi.org/10.1293/tox.2022-0093","url":null,"abstract":"<p><p>Our previous 4-week repeated dose toxicity study showed that wood preservative chromated copper arsenate (CCA) induced hepatocellular hypertrophy accompanied by biochemical hepatic dysfunction and an increase in oxidative stress marker, 8-hydroxydeoxyguanosine, in female rats. To further explore the molecular mechanisms of CCA hepatotoxicity, we analyzed 10%-buffered formalin-fixed liver samples from female rats for cell proliferation, apoptosis, and protein glutathionylation and conducted microarray analysis on frozen liver samples from female rats treated with 0 or 80 mg/kg/day of CCA. Chemical analysis revealed that dimethylated arsenical was the major metabolite in liver tissues of male and female rats. CCA increase labeling indices of proliferating cell nuclear antigen and decrease terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling accompanied with increased expression of protein glutathionylation, indicating a decrease in glutathione (GSH) in hepatocytes of female rats. Microarray analysis revealed that CCA altered gene expression of antioxidants, glutathione-S-transferase (GST), heat shock proteins and ubiquitin-proteasome pathway, cell proliferation, apoptosis, DNA methylation, cytochrome P450, and glucose and lipid metabolism in female rats. Increased expression of GSTs, including <i>Gsta2</i>, <i>Gsta3</i>, <i>Mgst1</i>, and <i>Cdkn1b</i> (<i>p27</i>), and decreased expression of the antioxidant <i>Mt1</i>, and DNA methylation <i>Dnmt1</i>, <i>Dnmt3a</i>, and <i>Ctcf</i> were confirmed in the liver of female rats in a dose-dependent manner. Methylation status of the promoter region of the <i>Mt1</i> was not evidently changed between control and treatment groups. The results suggested that CCA decreased GSH and altered the expression of several genes, including antioxidants, GST, and DNA methylation, followed by impaired cell proliferation in the liver of female rats.</p>","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"36 1","pages":"31-43"},"PeriodicalIF":1.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e4/80/tox-36-031.PMC9837468.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10585369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spontaneous mandibular follicular ameloblastoma in a female Sprague-Dawley rat","authors":"Juan LI, Guojian JIANG, Jie ZHANG, Zhuolin OU, Xin WU, Yueshu LIU","doi":"10.1293/tox.2023-0072","DOIUrl":"https://doi.org/10.1293/tox.2023-0072","url":null,"abstract":"Ameloblastoma is a locally aggressive tumor derived from the odontogenic epithelium of the developing tooth germ. It is rarely reported in experimental Sprague-Dawley (SD) rats. In this 90-day percutaneous repeated-dose toxicity study, mandibular nodules were observed from day 56 to 90. Upon necropsy, a well-demarcated nodule, approximately 1.2 × 1.0 × 1.0 cm, was found attached to the mandibular bone, alongside the unerupted left incisor. Histopathologically, the epithelial cells formed islands, nests, or anastomosing strands. The epithelial islands were surrounded by a peripheral layer of tall columnar cells with antibasilar nuclei arranged in a palisading pattern. Several mitotic cells were observed. Some epithelial islands displayed cystic degenerative changes and squamous metaplasia. Necrotic tissue with inflammatory cell infiltration was observed at the tumor margins. Immunohistochemically, the neoplastic epithelial islands and mesenchymal components exhibited positivity for pan-cytokeratin and vimentin, respectively. Based on these features, the case was diagnosed as follicular ameloblastoma in an SD rat.","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"68 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135611527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and efficacy of a novel robotic, fractional micro-coring device in a swine model.","authors":"Yuval Ramot,&nbsp;Udi Vazana,&nbsp;Orna Cacical,&nbsp;Abraham Nyska","doi":"10.1293/tox.2022-0079","DOIUrl":"https://doi.org/10.1293/tox.2022-0079","url":null,"abstract":"<p><p>Laser resurfacing may be accompanied by unwanted side effects. The micro coring technology, designed to remove small skin columns, was developed to avoid the thermal injury associated with lasers. However, very limited data are available on its pre-clinical efficacy and safety. The novel robotic, fractional micro-coring device, Aime^TM, was tested on four pigs, each treated in 12 sites, at 6 time-points, over the course of 28 days. Macroscopic and microscopic evaluation was performed at each of the 6 time-points during the 28-day follow-up. Macroscopically, treatment resulted in erythema and mild edema that quickly resolved. Microscopically, there was progressive re-coverage of the tested sites with complete, well differentiated, newly formed epidermis, associated with efficient elimination of the underlying excised dermis, which was replaced by maturing fibroplasia. Some of the sites demonstrated complete healing already after 7 days. No significant adverse events were noted with the use of the device. The use of the micro-coring device Aime^TM in a porcine model for skin fractional micro-excision and resurfacing was effective and safe. The comprehensive gradual healing process shown in this study with detailed histopathological images can also serve as a basis for future pre-clinical studies of fractional ablative devices.</p>","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"36 1","pages":"11-19"},"PeriodicalIF":1.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0a/54/tox-36-011.PMC9837470.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10577949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}