{"title":"Spontaneous bilateral thyroid follicular cell carcinoma (subtype: compact cellular carcinoma) with C-cell complexes in a male beagle.","authors":"Shingo Miyazaki, Takashi Ogawa, Tomoya Onozato, Yuji Okuhara, Tatsuya Nagasawa, Morimichi Hayashi","doi":"10.1293/tox.2024-0072","DOIUrl":"10.1293/tox.2024-0072","url":null,"abstract":"<p><p>We report the features of spontaneous bilateral thyroid follicular cell carcinoma in a 10-year-old male beagle. Necropsy revealed bilateral masses on the trachea, corresponding to the left and right sides of the thyroid gland. The masses were elastic, encapsulated, and distinct, with no connecting tumor tissues between them. Histologically, the tumor cells exhibited a predominant sheet-like growth pattern in both masses, and small follicular structures containing colloids were observed. Immunohistochemically, >50% of the tumor cells were positive for thyroglobulin. In the sheet-like growth area, all tumor cells were positive for cytokeratin and approximately 50% of them were positive for vimentin. The tumor cells were negative for calcitonin and parathormone. Electron microscopy of the tumor cells revealed colloid droplets and lysosomes in the cytoplasm, which are characteristics of follicular cells of the thyroid gland, although they were abnormally shaped and smaller in size compared to the normal cells. Many calcitonin-positive C cells were observed in the nodule area without a capsule in the left mass and were scattered within the tumor in the right mass. C cells were found individually and were negative for Ki-67 expression. Therefore, each of these cells was deemed to be derived from an individual C-cell complex. Based on these morphological features, the tumor was diagnosed as spontaneous bilateral thyroid follicular cell carcinoma of the compact cellular carcinoma subtype. This is the first report of electron microscopic findings and co-expression of cytokeratin and vimentin in thyroid follicular cell carcinoma in beagles.</p>","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"38 1","pages":"83-91"},"PeriodicalIF":0.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11745505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007385","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":"Current status of veterinary forensic science in Japan.","authors":"Tokuma Yanai","doi":"10.1293/tox.2024-0041","DOIUrl":"10.1293/tox.2024-0041","url":null,"abstract":"<p><p>In Japan, forensic medicine was established in the early 1900s to investigate potential criminal activities. However, only a few veterinary courses in forensic science are available, and the training of forensic specialists has lagged. This study aimed to review the current status of veterinary forensic medicine in Japan. Veterinary forensics has recently been established, along with the publication of textbooks on animal abuse and wildlife forensics. Veterinary forensics can be broadly divided into the following categories: 1) criminal science, which includes the identification of animal abuse and neglect, and the responses to lawsuits; 2) monitoring of food safety and zoonosis; and 3) determination of the cause of death to support wildlife conservation efforts (wildlife forensics). The target animal species include mammals, reptiles, amphibians, and honeybees. To elucidate animal abuse, postmortem computed tomography and histopathological examinations are employed to determine the factors that lead to death.</p>","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"38 1","pages":"3-16"},"PeriodicalIF":0.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11745499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007301","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}
Marcia E Pereira Bacares, Edward L Stevens, Victoria Laast, Vimala Vemiredi, Hibret A Adissu, Mark G Mense
{"title":"Histopathology of incidental non-neoplastic findings in transgenic CByB6F1-Tg(HRAS)2Jic mice used in toxicity studies.","authors":"Marcia E Pereira Bacares, Edward L Stevens, Victoria Laast, Vimala Vemiredi, Hibret A Adissu, Mark G Mense","doi":"10.1293/tox.2024-0037","DOIUrl":"10.1293/tox.2024-0037","url":null,"abstract":"<p><p>This technical report presents a collection of illustrative images and concise descriptions of non-neoplastic microscopic findings noted in transgenic CByB6F1-Tg(HRAS)2Jic (Tg.rasH2) mice from 26-week-carcinogenicity studies. A unique finding in the Tg.rasH2 strain was the skeletal muscle myopathy observed in nearly all animals, particularly affecting the <i>femoralis</i> and <i>pectoralis</i> muscles, diaphragm, and subcutaneous muscles. Pigment was noted in various organs, particularly in the spleen due to the C57BL/6J background. Mononuclear and/or mixed cell inflammatory infiltrates occurred in various tissues, with or without secondary changes, similar to other rodent and non-rodent laboratory species. Vascular anomalies were sporadically noted, mainly in the uterus. Other notable findings included extramedullary hematopoiesis in the spleen; alveolar macrophage infiltrate (often with eosinophilic crystals) in the lung; and proliferative findings in several tissues, such as the lung (bronchiolo-alveolar hyperplasia), adrenal cortex (subcapsular hyperplasia), and uterus (cystic-endometrial hyperplasia). This paper also includes illustrations of other less frequently incidental findings. The information presented in this manuscript aims to serve as a valuable reference for pathologists and researchers and expected to offer contextual insights for carcinogenicity and other toxicological studies utilizing this animal model.</p>","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"38 1","pages":"93-111"},"PeriodicalIF":0.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11745503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007322","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":"Identification and characterization of spontaneous AA amyloidosis in CD-1 mice used in toxicity studies: implications of SAA1 and SAA2 copy number variations.","authors":"Mao Mizukawa, Kohei Tanaka, Akane Kashimura, Yu Uchida, Takanori Shiga, Naoyuki Aihara, Junichi Kamiie","doi":"10.1293/tox.2024-0070","DOIUrl":"10.1293/tox.2024-0070","url":null,"abstract":"<p><p>Amyloidosis is characterized by the extracellular deposition of insoluble protein fibrils that cause cellular damage and dysfunction in organs and tissues. Multiple types of amyloidosis and their causative precursor proteins have been identified in humans and animals. In toxicological studies, a high incidence of spontaneous amyloidosis has been reported in CD-1 mice; however, the precursor protein responsible remains unclear. In contrast, B6C3F1 mice have a low incidence of amyloidosis. This study aimed to identify the types of amyloidosis and causative precursor proteins in CD-1 mice and investigate the role of copy number variations (CNVs) in genes encoding precursor proteins in different mouse species. Histopathological examination revealed amyloids in multiple organs, which were confirmed by direct fast scarlet staining. Immunohistochemistry and liquid chromatography-tandem mass spectrometry analyses revealed that the deposition was derived from serum amyloid A (SAA1 and 2), suggesting that the CD-1 mice had AA amyloidosis. Copy number variation assays demonstrated higher copy numbers of SAA1 and SAA2 in CD-1 mice with amyloidosis than in C3H/He mice (the parent strain of B6C3F1 mice). These findings suggest that the high copy numbers of SAA1 and SAA2 may contribute to the high incidence of AA amyloidosis in CD-1 mice. This study examined spontaneous amyloidosis in CD-1 mice and revealed the correlation between SAA1 and SAA2 CNVs in the pathogenesis of the disease and the genetic factors influencing amyloidosis in mice.</p>","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"38 1","pages":"69-82"},"PeriodicalIF":0.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11745502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007380","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":"Metabolism and effects of acetoaceto-o-toluidine in the urinary bladder of humanized-liver mice","authors":"Shugo SUZUKI, Min GI, Yukie YANAGIBA, Nao YONEDA, Shotaro UEHARA, Yuka YOKOTA, Ikue NOURA, Masaki FUJIOKA, Arpamas VACHIRAARUNWONG, Anna KAKEHASHI, Shigeki KODA, Hiroshi SUEMIZU, Hideki WANIBUCHI","doi":"10.1293/tox.2024-0042","DOIUrl":"https://doi.org/10.1293/tox.2024-0042","url":null,"abstract":"</p><p>Occupational exposure to aromatic amines is a major risk factor for urinary bladder cancer. Our previous studies showed that acetoaceto-<i>o</i>-toluidine, which is produced using <i>o</i>-toluidine as a raw material, promotes urinary bladder carcinogenesis in rats. We also found high concentrations of <i>o</i>-toluidine, a human bladder carcinogen, in the urine of acetoaceto-<i>o</i>-toluidine-treated rats, indicating that urinary <i>o</i>-toluidine derived from acetoaceto-<i>o</i>-toluidine may play an important role in bladder carcinogenesis. However, this has not been investigated in humans. In the present study, we used non-humanized (F1-TKm30 mice) and humanized-liver mice established by human hepatocyte transplantation to compare differences in urinary acetoaceto-<i>o</i>-toluidine metabolites produced by human and mouse liver cells. We also examined the changes in acetoaceto-<i>o</i>-toluidine-induced mRNA expression in the liver and the proliferative effects on the bladder epithelium. Urinary <i>o</i>-toluidine was detected in both non-humanized and humanized mice. Acetoaceto-<i>o</i>-toluidine metabolites in the urine, cell proliferation activities, and DNA damage in the bladder urothelium were similar in non-humanized and humanized-liver mice. RNA expression analysis revealed that CYP1A2 expression increased in the livers of humanized-liver mice, and Cyp2c29 expression (equivalent to human CYP2C9/19) increased in the livers of non-humanized mice. These data suggest that acetoaceto-<i>o</i>-toluidine may be a human carcinogen, as evidenced by the detection of urinary <i>o</i>-toluidine in acetoaceto-<i>o</i>-toluidine-treated humanized-liver mice. This animal model is important for extrapolating toxicity data from animals to humans.</p>\u0000<p></p>","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"221 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249051","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":"High mobility group box1 as a danger signal inducing the infiltration of neutrophils and macrophages in thioacetamide-induced rat liver injury","authors":"Mizuki KURAMOCHI, Mohammad Rabiul KARIM, Takeshi IZAWA, Mitsuru KUWAMURA, Jyoji YAMATE","doi":"10.1293/tox.2024-0055","DOIUrl":"https://doi.org/10.1293/tox.2024-0055","url":null,"abstract":"</p><p>The liver, a major organ involved in substance metabolism, is highly susceptible to toxicity induced by chemicals and their metabolites. Although damage-associated molecular patterns (DAMPs) have been implicated in the development of sterile inflammation following cell injury, their involvement in chemically induced hepatocellular injury remains underexplored. This study aimed to determine the role of high-mobility group box 1 (HMGB1), a DAMP, in a rat model of liver injury treated with thioacetamide, a hepatotoxicant. The rats were administered thioacetamide and treated with HMGB1 neutralizing antibody. Histopathological analysis revealed the absence of significant differences between control rats and HMGB1 neutralizing antibody-treated rats. However, HMGB1 neutralizing antibody-treated rats showed a reduction in the hepatic devitalization enzymes, a decrease in the number of anti-inflammatory cluster of differentiation 163<sup>+</sup> M2 macrophages and neutrophils in the injured area, and a decrease in cytokine expression. These results suggest that HMGB1 leads to the progression of inflammation after chemically induced hepatocyte injury and may represent a therapeutic target for mitigating such injury.</p>\u0000<p></p>","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"38 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249050","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}
Yuumi AWAZUHARA, Yuki TOMONARI, Hiroko KOKOSHIMA, Yumi WAKO, Takuya DOI
{"title":"Lymphangiomas with the presence of erythrocytes in mesenteric lymph nodes of Wistar Hannover rats","authors":"Yuumi AWAZUHARA, Yuki TOMONARI, Hiroko KOKOSHIMA, Yumi WAKO, Takuya DOI","doi":"10.1293/tox.2024-0007","DOIUrl":"https://doi.org/10.1293/tox.2024-0007","url":null,"abstract":"</p><p>We performed morphological and immunohistochemical analyses of erythrocyte-rich vascular proliferative lesions of mesenteric lymph nodes in six male and one female Wistar Hannover rats. These lesions are conventionally diagnosed as hemangiomas due to abundant erythrocytes. Immunostaining was positive for prospero-related homeobox 1 (Prox-1) and/or vascular endothelial growth factor receptor 3 (VEGFR3) in all lesions, suggesting a lymphangitic origin. In 6 of 7 lesions, von Willebrand factor (vWF) immunostaining was negative, suggesting a non-blood vascular origin. These results demonstrated that almost all hemangiomas in rat mesenteric lymph nodes were lymphangiomas. To the best of our knowledge, this is the first report highlighting the lymphatic origin of vascular proliferative lesions in the mesenteric lymph nodes of rats.</p>\u0000<p></p>","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"15 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142184608","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":"Histopathology of spontaneous lesions in FVB/N mice","authors":"Atsuko MURAI, Chisato KANEKO, Hisakazu SANADA, Atsuhiko KATO","doi":"10.1293/tox.2024-0027","DOIUrl":"https://doi.org/10.1293/tox.2024-0027","url":null,"abstract":"</p><p>The FVB/N mouse strain is widely used in transgenic studies and as a model for autoimmune diseases. Although spontaneous lesions have been reported in aged FVB/N mice, information regarding younger FVB/N mice is lacking. This study aimed to investigate the spontaneous lesions in young FVB/N mice. Ten males and 10 females were necropsied at 10 and 26 weeks of age. All tissues were fixed in 10% neutral-buffered formalin, embedded in paraffin, and stained with hematoxylin and eosin. Histopathological examination revealed atrophy of the outer retina in all mice of both ages, with atrophy of the inner nuclear layer at 26 weeks. This ocular lesion is consistent with an autosomal recessive disorder in FVB/N mice. Decreased cellularity in the epiphyseal cartilage plate, reduced bone in the primary spongiosa of the femur, increased cellularity of lymphocytes in the thymus, dilatation of ducts in the mammary glands, and foveolar hyperplasia in the stomach were observed, all of which were indicative of age-related changes. These findings provide valuable background data for future studies using FVB/N mice.</p>\u0000<p></p>","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"28 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142184606","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}
Lingya XIA, Hai YUAN, Zhao GAO, Ying LV, Liang XU, Fengqi HU
{"title":"The role of mitochondrial reactive oxygen species in initiating mitochondrial damage and inflammation in wasp-venom-induced acute kidney injury","authors":"Lingya XIA, Hai YUAN, Zhao GAO, Ying LV, Liang XU, Fengqi HU","doi":"10.1293/tox.2024-0046","DOIUrl":"https://doi.org/10.1293/tox.2024-0046","url":null,"abstract":"</p><p>Acute kidney injury induced by stings from multiple wasps is a medical emergency and is a driving factor of acute renal dysfunction. Numerous studies have shown that mitochondrial reactive oxygen species (mtROS) play a key role in ischemia-reperfusion injury-, cisplatin-, and sepsis-induced acute kidney injury. However, the role of mtROS and its underlying mechanisms in wasp-venom-induced acute kidney injury remain inconclusive. In this study, we investigated the role and mechanisms of mtROS in mitochondrial damage and inflammation in a mouse model of acute kidney injury induced using wasp venom. Changes in mitochondrial function, transcription factor A (TFAM) expression, and DNA maintenance levels, renal function, stimulator of interferon gene (STING) expression, and inflammatory mediator levels in model mice with or without the mtROS scavenger Mito-Tempo were analyzed <i>in vivo</i>. Downregulation of mtROS levels reversed renal damage and mitochondrial dysfunction, and reduced STING expression and inflammation in the kidneys of model mice. The suppression of mtROS levels also improved the decrease in TFAM levels and mitochondrial DNA copy numbers in the kidneys of the model mice. In summary, the existing evidence in this study shows that mtROS contribute significantly to mitochondrial damage and inflammation in acute kidney injury induced by wasp venom.</p>\u0000<p></p>","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"179 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142184605","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":"The relationship between spontaneous cystic degeneration and pseudocapillarization in sinusoids in the liver of aged Sprague-Dawley rats","authors":"Atsushi SHIGA, Chinatsu FUJIWARA, Yoshitaka KATOH, Tsuyoshi ITO, Aya OHNUMA-KOYAMA, Naofumi TAKAHASHI, Takanori HARADA","doi":"10.1293/tox.2024-0034","DOIUrl":"https://doi.org/10.1293/tox.2024-0034","url":null,"abstract":"</p><p>Cystic degeneration (CD) in the liver is a cyst-like lesion composed of one or more pseudocysts lacking lining cells, occurring spontaneously in rats older than 12 months, with a male predilection. In this study, 32 CDs were identified in 23 out of 104 non-treated, control male Sprague-Dawley rats from two combined chronic toxicity and carcinogenicity studies with agrochemicals. They were examined histologically, histochemically, and immunohistochemically to assess the pathogenesis and pathological significance of CD, focusing on pseudocapillarization in aged rat liver. Pseudocapillarization refers to age-related capillarization of hepatic sinusoids and is distinct from sinusoidal capillarization observed in hepatic cirrhosis. Both CD and pseudocapillarization, characterized by factor VIII-related antigen expression, were primarily noted in the periportal regions of the rat liver. CD areas exhibited enhanced vimentin expression in a diffuse linear pattern in their septa with occasional focal linear α-smooth muscle actin expression and the fluid containing hyaluronic acid accumulated in their lumen that are thought to be formed by hepatocellular apoptosis. These findings suggest a series of reactive changes associated with hepatocellular apoptosis due to pseudocapillarization in the sinusoids. In conclusion, spontaneous CD in rat liver is not a degenerative lesion or cystic enlargement of stellate cells, but a structural abnormality in pre-existing liver tissue resulting from aging-related changes in sinusoidal endothelial cells and hepatocytes. Pseudocapillarization of sinusoids is considered a precursor lesion of CD in the rat liver.</p>\u0000<p></p>","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"22 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142184607","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}