Journal of Toxicologic Pathology最新文献_第7页

Application of convolutional neural network for analyzing hepatic fibrosis in mice. 卷积神经网络在小鼠肝纤维化分析中的应用。

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2023-01-01 DOI: 10.1293/tox.2022-0066

Hyun-Ji Kim, Eun Bok Baek, Ji-Hee Hwang, Minyoung Lim, Won Hoon Jung, Myung Ae Bae, Hwa-Young Son, Jae-Woo Cho

{"title":"Application of convolutional neural network for analyzing hepatic fibrosis in mice.","authors":"Hyun-Ji Kim, Eun Bok Baek, Ji-Hee Hwang, Minyoung Lim, Won Hoon Jung, Myung Ae Bae, Hwa-Young Son, Jae-Woo Cho","doi":"10.1293/tox.2022-0066","DOIUrl":"https://doi.org/10.1293/tox.2022-0066","url":null,"abstract":"Recently, with the development of computer vision using artificial intelligence (AI), clinical research on diagnosis and prediction using medical image data has increased. In this study, we applied AI methods to analyze hepatic fibrosis in mice to determine whether an AI algorithm can be used to analyze lesions. Whole slide image (WSI) Sirius Red staining was used to examine hepatic fibrosis. The Xception network, an AI algorithm, was used to train normal and fibrotic lesion identification. We compared the results from two analyses, that is, pathologists' grades and researchers' annotations, to observe whether the automated algorithm can support toxicological pathologists efficiently as a new apparatus. The accuracies of the trained model computed from the training and validation datasets were greater than 99%, and that obtained by testing the model was 100%. In the comparison between analyses, all analyses showed significant differences in the results for each group. Furthermore, both normalized fibrosis grades inferred from the trained model annotated the fibrosis area, and the grades assigned by the pathologists showed significant correlations. Notably, the deep learning algorithm derived the highest correlation with the pathologists' average grade. Owing to the correlation outcomes, we conclude that the trained model might produce results comparable to those of the pathologists' grading of the Sirius Red-stained WSI fibrosis. This study illustrates that the deep learning algorithm can potentially be used for analyzing fibrotic lesions in combination with Sirius Red-stained WSIs as a second opinion tool in non-clinical research.","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"36 1","pages":"21-30"},"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/c2/9e/tox-36-021.PMC9837472.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10585372","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}

引用次数: 0

Primary epididymis squamous cell carcinoma in a CB6F1-Tg rasH2 mouse. CB6F1-Tg rasH2小鼠原发性附睾鳞状细胞癌。

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2022-10-01 Epub Date: 2022-06-30 DOI: 10.1293/tox.2022-0047

Manabu Ikeda, Toshihisa Fujiwara, Junko Fujishima, Airo Yukawa, Kinji Kobayashi

{"title":"Primary epididymis squamous cell carcinoma in a CB6F1-Tg rasH2 mouse.","authors":"Manabu Ikeda, Toshihisa Fujiwara, Junko Fujishima, Airo Yukawa, Kinji Kobayashi","doi":"10.1293/tox.2022-0047","DOIUrl":"https://doi.org/10.1293/tox.2022-0047","url":null,"abstract":"In a 26-week carcinogenicity study in rasH2-Tg mice, squamous cell carcinoma on the epididymis was observed in a male mouse in the positive control group treated with N-methyl-N-nitrosourea. A 29-week-old male rasH2-Tg mouse that was euthanized 21 weeks after the administration of N-methyl-N-nitrosourea had a white-grayish mass on the left caput epididymis. The mass was nodular and consisted of pleomorphic tumor cells forming alveolar, sheeted, and trabecular structures suggesting epithelial tumor growth. These cells presented a cobblestone-like arrangement and formed intercellular bridges. Keratinization was infrequently observed. Periodic acid-methenamine-silver staining revealed argyrophilic fibrous structures around the alveolar structure of the tumor cells. Immunohistochemically, the tumor cells were positive for cytokeratin AE1/AE3 and cytokeratin 14 and negative for cytokeratin 5, p63, uroplakin III, vimentin, desmin, and αSMA. These immunohistochemical results suggested the tumor cells originated from the epididymal ducts. Metastatic lesions were observed in the mesenteric, inguinal, and pancreaticoduodenal lymph nodes. Based on these results, this tumor was diagnosed to be a primary squamous cell carcinoma of the epididymis. This is the first report of primary squamous cell carcinoma of the epididymis in a rasH2-Tg mouse.","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"35 4","pages":"349-353"},"PeriodicalIF":1.2,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4d/60/tox-35-349.PMC9647212.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40475883","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}

引用次数: 0

Changes in 5-Fluorouracil-induced external granular cell damage during the time-course of the developing cerebellum of infant rats. 5-氟尿嘧啶诱导的幼鼠小脑外颗粒细胞损伤在时间过程中的变化。

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2022-10-01 Epub Date: 2022-05-30 DOI: 10.1293/tox.2022-0003

Yuko Yamaguchi, Tsubasa Saito, Mizuho Takagi, Tomomi Nakazawa, Kazutoshi Tamura

{"title":"Changes in 5-Fluorouracil-induced external granular cell damage during the time-course of the developing cerebellum of infant rats.","authors":"Yuko Yamaguchi, Tsubasa Saito, Mizuho Takagi, Tomomi Nakazawa, Kazutoshi Tamura","doi":"10.1293/tox.2022-0003","DOIUrl":"https://doi.org/10.1293/tox.2022-0003","url":null,"abstract":"5-Fluorouracil (5-FU) is widely used as a chemotherapeutic agent that blocks DNA synthesis and replication by inhibiting thymidylate synthetase. This study aimed to elucidate 5-FU-induced changes in the external granular cells (EGCs) in the cerebellum of infant rats and the possible underlying mechanism. Six-day-old infant rats were injected subcutaneously with 40 mg/kg of 5-FU, and their cerebellums were examined at 6, 9, 12, and 24 h after treatment (HAT), and 2, 4, and 10 d after treatment (DAT). The width of the external granular layer (EGL) decreased from 24 HAT to 4 DAT in the 5-FU group compared to that in the control group. However, the width in the 5-FU group was comparable to that of the control group at 10 DAT. The number of apoptotic cells, cleaved caspase 3-labeling index (LI%), p21cip1-LI%, and expression levels of p53, p21cip1, and Fas mRNAs increased at 24 HAT. However, no changes were detected in the expression levels of Puma and Bax mRNAs at any time point. BrdU-LI% increased at 6 and 12 HAT but decreased at 24 HAT. The phospho-histone H3-LI% decreased from 6 HAT to 2 DAT. The width of the molecular layer decreased compared to that of the control group at 10 DAT. No differences were observed in Purkinje cell development. These results indicate that 5-FU inhibited cell proliferation by inducing apoptosis of EGCs via activation of Fas and caspase-3 without the involvement of the mitochondrial pathway and induced p53-dependent G1-S and G2-M phase arrest.","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"35 4","pages":"299-311"},"PeriodicalIF":1.2,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/51/f3/tox-35-299.PMC9647215.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40475884","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}

引用次数: 1

Kidney organoid derived from renal tissue stem cells is a useful tool for histopathological assessment of nephrotoxicity in a cisplatin-induced acute renal tubular injury model. 来源于肾组织干细胞的肾类器官是对顺铂诱导的急性肾小管损伤模型肾毒性进行组织病理学评估的有用工具。

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2022-10-01 Epub Date: 2022-07-18 DOI: 10.1293/tox.2022-0006

Shota Ueno, Kenji Kokura, Yasushi Kuromi, Mitsuhiko Osaki, Futoshi Okada, Shinji Kitamura, Tetsuya Ohbayashi

{"title":"Kidney organoid derived from renal tissue stem cells is a useful tool for histopathological assessment of nephrotoxicity in a cisplatin-induced acute renal tubular injury model.","authors":"Shota Ueno, Kenji Kokura, Yasushi Kuromi, Mitsuhiko Osaki, Futoshi Okada, Shinji Kitamura, Tetsuya Ohbayashi","doi":"10.1293/tox.2022-0006","DOIUrl":"https://doi.org/10.1293/tox.2022-0006","url":null,"abstract":"Organoids derived from renal tissue stem cells (KS cells) isolated from the S3 segment of adult rat nephrons have previously been developed and evaluated. However, data regarding the histopathological evaluation of these organoids are limited. Therefore, in this study, we performed histopathological examinations of the properties of these organoids and evaluated the nephrotoxicity changes induced by cisplatin treatment. We observe that the tubular structure of the organoids was generally lined by a single layer of cells, in concordance with previous findings. Microvilli were exclusively observed under electron microscopy on the luminal side of this tubular structure. Moreover, the luminal side of the tubular structure was positive for aquaporin-1 (Aqp1), a marker of the proximal renal tubule. Cisplatin treatment induced cell death and degeneration, including cytoplasmic vacuolation, in cells within the tubular structure of the organoids. Cisplatin toxicity is associated with the induction of γ-H2AX (a marker of DNA damage) and the drop of phospho-histone H3 (a marker of cell division) levels. During the nephrotoxicity assessment, the kidney organoids displayed various features similar to those of the natural kidney, suggesting that it is possible to use these organoids in predicting nephrotoxicity. The histological evaluation of the organoids in this study provides insights into the mechanisms underlying nephrotoxicity.","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"35 4","pages":"333-343"},"PeriodicalIF":1.2,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/dd/b8/tox-35-333.PMC9647211.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40478341","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}

引用次数: 0

In vivo screening of subcutaneous tolerability for the development of novel excipients. 为开发新的赋形剂进行皮下耐受性的体内筛选。

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2022-10-01 Epub Date: 2022-06-10 DOI: 10.1293/tox.2022-0035

Yuichi Takai, Stephanie Powlin, Yasuyuki Awasaki, Toshiaki Yamauchi, Tomoya Sano, Haruyuki Takahashi, Abdul-Hackam Ranneh, Yuta Arai

{"title":"In vivo screening of subcutaneous tolerability for the development of novel excipients.","authors":"Yuichi Takai, Stephanie Powlin, Yasuyuki Awasaki, Toshiaki Yamauchi, Tomoya Sano, Haruyuki Takahashi, Abdul-Hackam Ranneh, Yuta Arai","doi":"10.1293/tox.2022-0035","DOIUrl":"https://doi.org/10.1293/tox.2022-0035","url":null,"abstract":"To develop safe subcutaneous formulations and minimize the risk of local irritation, it is essential to optimize the composition of active pharmaceutical ingredients and excipients. Depending on the physicochemical properties of the active pharmaceutical ingredient, additional excipients may be required to improve the stability and solubility of the active pharmaceutical ingredient. However, some of these excipients may not have been previously used in injectable drugs. Owing to the lack of safety data for such excipients, especially those used in subcutaneous dosing, it is important to evaluate their potential for local irritation during the early stages of formulation development. We evaluated the tolerability of 44 formulations with 24 candidate novel excipients, such as surfactants, polymers, and lipids, in a single subcutaneous dose in rats. Excipient formulations were administered as single bolus subcutaneous injections with an injection volume of 1 mL. The injection sites were observed for 2 days, and macroscopic and microscopic examinations were conducted. Local tolerability was evaluated on the basis of severity, incidence, and pathophysiology of each finding. Formulations that caused tissue degeneration or necrosis, which is indicative of tissue injury, were determined to be irritative and poorly tolerated. A single-dose subcutaneous screening study in rats was considered effective in ranking the safety of candidate excipients during the formulation optimization phase.","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"35 4","pages":"355-360"},"PeriodicalIF":1.2,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/75/bd/tox-35-355.PMC9647210.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40475882","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}

引用次数: 0

Inflammation of the cardiac coronary artery in ICR mice. ICR小鼠心脏冠状动脉炎症。

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2022-10-01 Epub Date: 2022-06-11 DOI: 10.1293/tox.2022-0022

Kyohei Yasuno, Masako Imaoka, Tetsuya Ohsawa, Keiko Okado, Kiyonori Kai, Yoshimi Tsuchiya

{"title":"Inflammation of the cardiac coronary artery in ICR mice.","authors":"Kyohei Yasuno, Masako Imaoka, Tetsuya Ohsawa, Keiko Okado, Kiyonori Kai, Yoshimi Tsuchiya","doi":"10.1293/tox.2022-0022","DOIUrl":"https://doi.org/10.1293/tox.2022-0022","url":null,"abstract":"Inflammation of the cardiac coronary artery in ICR mice is occasionally observed in toxicity studies; however, this has not been well explored histologically. Herein, we investigated the detailed histology of the associated lesions in 6-8-week-old ICR mice. Coronary artery inflammation in the right ventricular wall was observed in 10 of 142 mice (7.0%). Histopathological examination revealed hypertrophy of the vascular smooth muscle cells and perivascular infiltration of macrophages in mild cases. In moderate to marked cases, single-cell necrosis of vascular smooth muscle cells, hemorrhage of the tunica media, and fibrinoid necrosis of the vessel wall were observed, in addition to the changes seen in mild cases. Electron microscopic examination of moderate cases revealed a discontinuous internal elastic lamina suggestive of rupture, and vascular smooth muscle cells beneath the elastic lamina showed degeneration and necrosis. These findings suggest that the lesions developed as a rupture of the internal elastic lamina and necrosis of vascular smooth muscle cells, while leaked plasma components caused vascular and perivascular inflammation. In ICR mice, dystrophic calcinosis (DCC) is known to occur rarely in the right ventricle. DCC is defined as focal calcification in necrotic myocardial fibers, the pathogenesis of which is considered to involve ectopic calcification. Since calcification was not observed in any part of the heart, including the inflammation region, the pathophysiology of cardiac arterial inflammation seen in our ICR mice was considered to differ from that of DCC.","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"35 4","pages":"345-348"},"PeriodicalIF":1.2,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/46/f5/tox-35-345.PMC9647214.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40478345","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}

引用次数: 0

Chemical-induced lung tumor in Tg-rasH2 mice: a novel mouse tumor model to assess immune checkpoint inhibitors combined with a chemotherapy drug. 化学物质诱导的 Tg-rasH2 小鼠肺肿瘤：评估免疫检查点抑制剂联合化疗药物的新型小鼠肿瘤模型。

IF 0.9 4区医学

Journal of Toxicologic Pathology Pub Date : 2022-10-01 Epub Date: 2022-06-26 DOI: 10.1293/tox.2022-0040

Teruaki Hagiwara, Takamasa Numano, Tomomi Hara, Taiki Sugiyama, Yukinori Mera, Seiko Tamano, Hiroto Miyata

{"title":"Chemical-induced lung tumor in Tg-rasH2 mice: a novel mouse tumor model to assess immune checkpoint inhibitors combined with a chemotherapy drug.","authors":"Teruaki Hagiwara, Takamasa Numano, Tomomi Hara, Taiki Sugiyama, Yukinori Mera, Seiko Tamano, Hiroto Miyata","doi":"10.1293/tox.2022-0040","DOIUrl":"10.1293/tox.2022-0040","url":null,"abstract":"In subcutaneous tumor models, changes in the tumor microenvironment can lead to differences in therapeutic treatment responses between the subcutaneous and parent tumors. Accordingly, we generated a lung carcinogenesis model that combines genetically modified mice (Tg-rasH2 mice) with two-stage chemical carcinogenesis as an alternative to the subcutaneous tumor model. In this model, Tg-rasH2 mice were treated with 1-ethyl-1-nitrosourea, followed by butylhydroxytoluene. Mice developed lung adenomas five weeks after treatment initiation. Subsequently, anti-mouse PD-1 antibody (α-mPD-1) or isotype control was administered intraperitoneally twice a week for 4 weeks. Tumor growth was examined by measuring the relative tumor area in serially sliced lung histopathological specimens. No statistically significant differences were observed in the relative lung tumor areas between treated and control groups. A second experiment then examined the antitumor efficacy of α-mPD-1 combined with gemcitabine in a mouse model. Mice were treated identically as in Experiment 1, except that the treated group received once-weekly intraperitoneal injections of 10 mg/kg gemcitabine. In contrast to Experiment 1, the combined treatment significantly reduced the relative tumor areas in the lungs. This result also resembles that of a phase III clinical trial (ORIENT-12), showing that patients with non-small-cell lung carcinoma benefited from combination treatment with gemcitabine and the anti-human PD-1 antibody sintilimab. Thus, this mouse model could be a feasible means to preclinically evaluate the antitumor efficacy of different immunotherapy and chemotherapy drug combinations.","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"35 4","pages":"321-331"},"PeriodicalIF":0.9,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/46/20/tox-35-321.PMC9647217.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40475881","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}

引用次数: 0

Honorary Member, Michihito Takahashi, M.D., Ph.D., 1937-2022. 名誉会员，高桥道仁，医学博士，1937-2022。

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2022-10-01 Epub Date: 2022-10-20 DOI: 10.1293/tox.2022-m1

引用次数: 0

Early detection of urinary bladder carcinogens in rats by immunohistochemistry for γ-H2AX: a review from analyses of 100 chemicals. 通过 γ-H2AX 免疫组织化学方法早期检测大鼠膀胱致癌物：对 100 种化学物质分析的综述。

IF 0.9 4区医学

Journal of Toxicologic Pathology Pub Date : 2022-10-01 Epub Date: 2022-08-18 DOI: 10.1293/tox.2022-0061

Takeshi Toyoda, Kumiko Ogawa

{"title":"Early detection of urinary bladder carcinogens in rats by immunohistochemistry for γ-H2AX: a review from analyses of 100 chemicals.","authors":"Takeshi Toyoda, Kumiko Ogawa","doi":"10.1293/tox.2022-0061","DOIUrl":"10.1293/tox.2022-0061","url":null,"abstract":"In safety evaluations of chemicals, there is an urgent need to develop short-term methods to replace long-term carcinogenicity tests. We have reported that immunohistochemistry for γ-H2AX, a well-established biomarker of DNA damage, can detect bladder carcinogens at an early stage using histopathological specimens from 28-day repeated-dose oral toxicity studies in rats. Given the markedly low level of γ-H2AX formation in the bladder urothelium of untreated rats, an increase in γ-H2AX-positive cells following chemical exposure can be relatively easy to identify. Among the 100 compounds examined to date, bladder carcinogens can be detected with high sensitivity (33/39; 84.6%) and specificity (58/61; 95.1%). As expected, γ-H2AX formation levels tended to be high following exposure to genotoxic bladder carcinogens, whereas nongenotoxic bladder carcinogens also increased the number of γ-H2AX-positive cells, probably through secondary DNA damage associated with sustained proliferative stimulation. γ-H2AX formation in the bladder urothelium reflects species differences in susceptibility to bladder carcinogenesis between rats and mice and shows a clear dose-dependency associated with the intensity of tumor development as well as high reproducibility. Some of the bladder carcinogens that showed false-negative results in the evaluation of γ-H2AX alone could be detected by combined evaluation with immunostaining for bladder stem cell markers, including aldehyde dehydrogenase 1A1. This method may be useful for the early detection of bladder carcinogens, as it can be performed by simple addition of conventional immunostaining using formalin-fixed paraffin-embedded tissues from 28-day repeated-dose toxicity studies in rodents, which are commonly used in safety evaluations of chemical substances.","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"35 4","pages":"283-298"},"PeriodicalIF":0.9,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/cc/6d/tox-35-283.PMC9647216.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40478344","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}

引用次数: 0

Lack of hepatocarcinogenicity of 2,2'-[1,2-ethanediylbis(oxymethylene)]bis-oxirane, 3-hydroxy-2-naphthoic acid, and acetoacetanilide in a medium-term rat liver bioassay. 在中期大鼠肝脏生物测定中，缺乏2,2'-[1,2-乙二基双(氧亚甲基)]双氧环烷，3-羟基-2-萘酸和乙酰乙酰苯胺的肝癌致癌性。

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2022-10-01 Epub Date: 2022-08-01 DOI: 10.1293/tox.2022-0010

Hiroshi Yamagata, Tsubasa Saito, Takezo Okamoto, Kensuke Satomoto, Tatsuya Mitsumoto, Atsushi Wakita, Maki Nakamura, Takahiro Hayashi, Yuichi Kuroiwa

{"title":"Lack of hepatocarcinogenicity of 2,2'-[1,2-ethanediylbis(oxymethylene)]bis-oxirane, 3-hydroxy-2-naphthoic acid, and acetoacetanilide in a medium-term rat liver bioassay.","authors":"Hiroshi Yamagata, Tsubasa Saito, Takezo Okamoto, Kensuke Satomoto, Tatsuya Mitsumoto, Atsushi Wakita, Maki Nakamura, Takahiro Hayashi, Yuichi Kuroiwa","doi":"10.1293/tox.2022-0010","DOIUrl":"https://doi.org/10.1293/tox.2022-0010","url":null,"abstract":"The carcinogenicity of 2,2'-[1,2-ethanediylbis(oxymethylene)]bis-oxirane (ethylene glycol diglycidyl ether; EGDE), 3-hydroxy-2-naphthoic acid (HNA), and acetoacetanilide (AAA) was investigated using a medium-term rat liver bioassay for an occupational safety assessment. F344 male rats were administered a single intraperitoneal injection of diethylnitrosamine (200 mg/kg body weight (bw)/day) and then starting 2 weeks later, they received EGDE at 6, 20, and 60 mg/kg bw/day, HNA at 20, 60, and 200 mg/kg bw/day, or AAA at 60, 200, and 600 mg/kg bw/day by oral gavage for 6 weeks. The animals in the positive control group received phenobarbital sodium solution (PB, 25 mg/kg bw/day) by oral gavage and those in the negative control group received a vehicle (water/corn oil) during the administration period of test substances in this model. All animals were subjected to two-thirds partial hepatectomy at week 3 and euthanized at week 8. Neither the number nor the area of hepatocellular foci positive for glutathione S-transferase placental form (GST-P) increased in any of the EGDE, HNA, or AAA treated groups. However, the number and area of GST-P-positive foci significantly increased in the positive control group treated with PB. The results indicate that EGDE, HNA, and AAA lack hepatocarcinogenicity in rats.","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"35 4","pages":"313-320"},"PeriodicalIF":1.2,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/24/61/tox-35-313.PMC9647213.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40478342","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}

引用次数: 0