Human & experimental toxicology最新文献

{"title":"Carvedilol alleviates the detrimental effects of azathioprine on hepatic tissues in experimental rats: Focusing on redox system, inflammatory and apoptosis pathways.","authors":"Abdel-Gawad S Shalkami, Ehab A M El-Shoura, Mohammed I A Hassan","doi":"10.1177/09603271241269003","DOIUrl":"10.1177/09603271241269003","url":null,"abstract":"<p><strong>Purpose: </strong>Drug-induced liver injury is becoming an increasingly important topic in drug research and clinical practice. Due to a lack of experimental animal models, predicting drug-induced liver injury in humans is challenging. Azathioprine (AZA) is a classical immunosuppressant with hepatotoxic adverse effects. The present study aimed to address the hepatoprotective effect of carvedilol (CAR) against AZA-induced hepatocellular injury via assessing redox-sensitive signals.</p><p><strong>Method: </strong>To achieve this purpose, rats were allocated into four groups: control, CAR only, AZA only, and CAR plus AZA groups. The induction of hepatic injury was induced by a single intraperitoneal injection of AZA at a dose of 50 mg/kg on the 6th day of the experiment. Each experimental protocol was approved and supervised by the Ethics Committee for Animal Experiments.</p><p><strong>Results: </strong>The results of the present study revealed that CAR administration significantly diminished AZA-induced hepatic dysfunction, as evidenced by relief of hepatic function biomarkers and histopathological aberration induced by AZA injection. Besides, CAR restored oxidant/antioxidant balance as well as NRF2 expression. In addition, CAR suppressed inflammatory response induced by AZA challenge as evidenced by downregulation of TLR4, TNF-α, MPO, and eNOS/iNOS levels in hepatic tissue. Moreover, CAR recovered apoptotic/anti-apoptotic status by modulation of caspase-3/Bcl2 expression.</p><p><strong>Conclusion: </strong>Taken together, CAR protects against AZA-induced hepatic injury via antioxidant, anti-inflammatory, and anti-apoptotic activities. These findings revealed that CAR could be a good candidate for hepatic injury protection and can be added to AZA therapeutic regimen to reduce their adverse effect.</p>","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"43 ","pages":"9603271241269003"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141857416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism of action of curcumin targeting TRPM2/NLRP3 signaling axis to mediate cell death in the treatment of knee osteoarthritis.","authors":"Kai Zhu, Jianping Bi, Qingkun Zhang, Yifan Yang, Jie Li, Yanchen Liang","doi":"10.1177/09603271241308798","DOIUrl":"https://doi.org/10.1177/09603271241308798","url":null,"abstract":"<p><strong>Objects: </strong>This study intends to explore the possible mechanisms of curcumin's action after knee osteoarthritis.</p><p><strong>Methods: </strong>Chondrocytes alone were used to mimic the cellular inflammatory response with interleukin IL-1β. Overexpressing TRPM2 chondrocytes were constructed using cell transfection technique for mechanism verification. The proliferation of chondrocytes was assessed by CCK8 assay, cellular ROS level was detected by flow cytometry, cellular inflammatory factor content was detected by ELISA kit, and molecules of cellular pyroptosis-related signaling pathway were detected by western blot and immunofluorescence. In vivo experiments, a rat knee osteoarthritis model was constructed. Cartilage integrity was assessed by histological analysis, cellular inflammatory factor content was detected by ELISA kit, and cellular pyroptosis-related signaling pathway molecules were detected by western blot and immunohistochemistry.</p><p><strong>Results: </strong>Curcumin targeting the TRPM2/NLRP3 signaling axis significantly inhibited IL-1β induced decrease in cell viability, increase in ROS level, secretion of inflammatory factors such as TNF-α, IL-6, IL-10, etc., as well as decreased the expression of cellular scaffolding-related proteins, such as GSDMD, NLRP3 and pro-caspase-1, etc. (<i>p</i> < .05). Meanwhile, curcumin targeting the TRPM2/NLRP3 signaling axis also significantly improved the pathological state of cartilage tissue, maintained cartilage integrity, and reduced the secretion of inflammatory factors, and treated osteoarthritis of the knee in rats by mediating cellular pyroptosis.</p><p><strong>Conclusions: </strong>Curcumin can effectively improve the inflammatory response of chondrocytes through the TRPM2/NLRP3 signaling axis in the treatment of osteoarthritis of the knee in rats.</p>","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"43 ","pages":"9603271241308798"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142831515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retrospective analysis of carcinogenicity assessments within FDA-notified GRAS determinations.","authors":"Khatera Rahmani, Yen-Ching Wu, Neil R Buck, Alexandria Lau, Paul R Hanlon","doi":"10.1177/09603271241254338","DOIUrl":"https://doi.org/10.1177/09603271241254338","url":null,"abstract":"<p><p>Frameworks have been developed to standardize the assessment of carcinogenic potential in the pharmaceutical and agrochemical industries, building upon decades of research. Carcinogenicity is also evaluated during the safety evaluation of food substances, using a comprehensive approach unique to each substance. To better understand these approaches, a retrospective assessment was conducted on the publicly available database of substances notified to the United States Food and Drug Administration (US FDA) as being Generally Recognized As Safe (GRAS). The data contained within these GRAS notifications (GRNs) were reviewed for the methods used to evaluate carcinogenic potential (genotoxicity studies, 2-year bioassays, other pre-clinical animal studies) to identify patterns that could provide an understanding of how this assessment has been conducted for different categories of food substances. While different approaches to the safety evaluation were required to adapt to the unique food substances, the data in all notifications supported the conclusion of safety. The evaluation of food substances for carcinogenic potential must consider all available data, including identifying the need for when more data must be generated to support an evaluation. Due to the complexity of substances used in food, ranging from defined chemical entities to minimally processed agricultural commodities to live microorganisms, the approach to conducting the safety evaluation of food substances must be able to adapt to the most relevant scientifically supported approach. This paper illustrates the data commonly used to support the safety of different types of food substances and proposes an approach familiar to other product sectors.</p>","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"43 ","pages":"9603271241254338"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141763552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histone demethylase PHF8 protected against chondrocyte injury and alleviated posttraumatic osteoarthritis by epigenetically enhancing WWP2 expression.","authors":"Xin Tang, Jingsheng He, Ye Hao","doi":"10.1177/09603271241292165","DOIUrl":"10.1177/09603271241292165","url":null,"abstract":"<p><p>Aberrant mechanical forces were considered as an important factor for osteoarthritis (OA) pathogenesis. Plant homeodomain finger-containing protein 8 (PHF8) participated in osteogenic differentiation and inflammatory progression. However, the role of PHF8 in aberrant force-related OA remains to be elucidated. In this study, a fluid shear stress (FSS) model in ATDC5 cells and an anterior cruciate ligament transection (ACLT) animal model were constructed. The results revealed the decrease of PHF8 in aberrant force-induced cartilage damage in vitro and in vivo. PHF8 overexpression alleviated the aberrant force-induced cell apoptosis, extracellular matrix degradation, and inflammation. Chromatin immunoprecipitation (ChIP) assays demonstrated that PHF8 epigenetically regulated WWP2 expression through demethylating H3K9me2 at WWP2 promoter, which was influenced by FSS treatment. C-X-C chemokine receptor type 4 (CXCR4) was identified as a potential substrate of WWP2. Co-immunoprecipitation (Co-IP) and ubiquitination experiments further demonstrated WWP2 decreased the stability of CXCR4 via the ubiquitination pathway. Subsequently, rescue experiments validated reintroduction of WWP2 significantly attenuated the effects of PHF8 deletion on FSS-induced chondrocyte injury, and CXCR4 overexpression reversed the protective effects of WWP2 overexpression on chondrocyte injury in FSS-treated ATDC5 cells. Moreover, delivery of a PHF8 adeno-associated virus (AAV) into articular cartilage remarkably ameliorated the breakdown of cartilage matrix by ACLT in mice. In conclusion, our findings highlighted the importance of PHF8/WWP2/CXCR4 signaling pathway in aberrant force-induced cartilage injury, which might provide a novel insight on future epigenetic-based treatment of posttraumatic OA.</p>","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"43 ","pages":"9603271241292165"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network pharmacology and experimental verification: Unraveling Zhiwei Fuwei Pills's role and mechanism in angiogenesis of precancerous lesions of gastric cancer.","authors":"Pengcheng Dou, Ruiping Song, Zhuangzhuang Feng, Bing Jiang, Xinyi Chen, Yuanbin Luo, Jiaojiao Zuo, Yi Gao, Jin Shu","doi":"10.1177/09603271241281159","DOIUrl":"https://doi.org/10.1177/09603271241281159","url":null,"abstract":"<p><strong>Objective: </strong>Precancerous lesions of gastric cancer (PLGC) are key pathological stages in the transformation of gastric \"inflammation-cancer\", and timely and effective intervention at this stage is of great importance in the prevention and treatment of gastric cancer. Zhiwei Fuwei Pills (ZWFW), as a traditional Chinese medicine formulation, has been proven to have good clinical efficacy in the treatment of PLGC, but its specific mechanism of action has not been fully explained. Thus, this study validated the efficacy and explored the potential mechanisms of ZWFW in treating PLGC by integrating network pharmacology analyses and experimental verification.</p><p><strong>Methods: </strong>The TCMSP database was used to obtain the active ingredients of ZWFW and their corresponding targets, and the GeneCards database was used to retrieve PLGC-related targets. The intersecting targets between ZWFW and PLGC were obtained through mapping, and protein-protein interaction (PPI) networks and \"drug-active ingredient-target\" networks were constructed by using Cytoscape software. The DAVID database was used for GO functional enrichment analysis and KEGG pathway enrichment analysis. AutoDockTools software was used for molecular docking of key active ingredients and key targets. In order to verify the analysis results of network pharmacology, TEM and H&E were used to observe the effects of different dosage groups of ZWFW on gastric mucosal microvasculature in PLGC rats. Subsequently, the ELISA, IF, IHC, RT-PCR and western blot were used to detected the expression levels of relevant targets in the tissues, so as to verify the potential mechanism of ZWFW in intervening PLGC.</p><p><strong>Results: </strong>After the screening, 258 effective active ingredients and 325 targets were obtained, and 1294 disease-related targets were determined, resulting in 139 intersection targets through mapping. The KEGG enrichment results showed that PI3K/Akt and HIF-1 signaling pathway might play important roles in the treatment mechanism of PLGC. The molecular docking results showed that active ingredients of ZWFW all had a strong affinity and stable structure with key targets, including AKT1 and VEGF. In vivo experiments confirmed that ZWFW could improve gastric mucosal microvascular abnormalities in PLGC, effectively intervene in gastric mucosal pathological grading. Meanwhile, compared with the model group, this formulation could reduce the expression levels of PI3K, Akt, mTOR, HIF-1α, and VEGF in gastric mucosa, showing a dose-effect relationship.</p><p><strong>Conclusion: </strong>ZWFW can intervene in the neovascularization and pathological evolution of PLGC, and this mechanism of action may be achieved by inhibiting abnormal activation of the PI3K/Akt/mTOR/HIF-1α/VEGF signaling pathway.</p>","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"43 ","pages":"9603271241281159"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142157049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gpnmb silencing protects against hyperoxia-induced acute lung injury by inhibition of mitochondrial-mediated apoptosis.","authors":"Xiaoqin Wang, Song Qin, Yingcong Ren, Banghai Feng, Junya Liu, Kun Yu, Hong Yu, Zhenliang Liao, Hong Mei, Mei Tan","doi":"10.1177/09603271231222873","DOIUrl":"10.1177/09603271231222873","url":null,"abstract":"<p><p><b>Background:</b> Hyperoxia-induced acute lung injury (HALI) is a complication to ventilation in patients with respiratory failure, which can lead to acute inflammatory lung injury and chronic lung disease. The aim of this study was to integrate bioinformatics analysis to identify key genes associated with HALI and validate their role in H₂O₂-induced cell injury model.<b>Methods:</b> Integrated bioinformatics analysis was performed to screen vital genes involved in hyperoxia-induced lung injury (HLI). CCK-8 and flow cytometry assays were performed to assess cell viability and apoptosis. Western blotting was performed to assess protein expression.<b>Results:</b> In this study, glycoprotein non-metastatic melanoma protein B (<i>Gpnmb</i>) was identified as a key gene in HLI by integrated bioinformatics analysis of 4 Gene Expression Omnibus (GEO) datasets (GSE97804, GSE51039, GSE76301 and GSE87350). Knockdown of <i>Gpnmb</i> increased cell viability and decreased apoptosis in H²O²-treated MLE-12 cells, suggesting that <i>Gpnmb</i> was a proapoptotic gene during HALI. Western blotting results showed that knockdown of <i>Gpnmb</i> reduced the expression of Bcl-2 associated X (BAX) and cleaved-caspase 3, and increased the expression of Bcl-2 in H₂O₂ treated MLE-12 cells. Furthermore, <i>Gpnmb</i> knockdown could significantly reduce reactive oxygen species (ROS) generation and improve the mitochondrial membrane potential.<b>Conclusion:</b> The present study showed that knockdown of <i>Gpnmb</i> may protect against HLI by repressing mitochondrial-mediated apoptosis.</p>","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"43 ","pages":"9603271231222873"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139081181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of combined exposure of manganese and iron on serum inflammatory factor levels among workers.","authors":"Dian-Yin Liang, Jian-Chao Peng, Bing-Yan Xie, Wen-Xia Qin, Michael Aschner, Shi-Yan Ou, Yue-Ming Jiang","doi":"10.1177/09603271241293112","DOIUrl":"https://doi.org/10.1177/09603271241293112","url":null,"abstract":"<p><strong>Objective: </strong>The aim of the study is to examine the association between long-term occupational exposure to Mn and Fe and their health effects in workers.</p><p><strong>Methods: </strong>108 Mn workers were selected for the Mn exposure groups; 92 non-Mn workers were in the control group. Inductively coupled plasma-mass spectrometry was used to determine the Mn and Fe concentration in the working environment. Graphite furnace-atomic absorption spectroscopy was used to determine the blood Mn concentration of workers. Serum inflammatory factors were measured by enzyme-linked immunosorbent assay.</p><p><strong>Results: </strong>The blood Mn concentration, positive rate of clinical symptoms and serum inflammatory response in the Mn exposure group was higher than in the control group.</p><p><strong>Conclusions: </strong>Low levels of Mn exposure may increase blood Mn concentrations, the rate of complaints of neurological symptoms and promote increased serum inflammatory response in workers.</p>","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"43 ","pages":"9603271241293112"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative analysis of noise and music exposure on inflammatory responses on lipopolysaccharide-induced septic rats.","authors":"Hu Liu, Xing-Guo Peng, Ran Gao, Kai Yang, Yan-Bo Zhao","doi":"10.1177/09603271241282584","DOIUrl":"https://doi.org/10.1177/09603271241282584","url":null,"abstract":"<p><strong>Objective: </strong>Environmental factors such as noise and music can significantly impact physiological responses, including inflammation. This study explored how environmental factors like noise and music affect lipopolysaccharide (LPS)-induced inflammation, with a focus on systemic and organ-specific responses.</p><p><strong>Materials and methods: </strong>24 Wistar rats were divided into four groups (<i>n</i> = 6 per group): Control group, LPS group, noise-exposed group, and music-exposed group. All rats, except for the Control group, received 10 mg/kg LPS intraperitoneally. The rats in the noise-exposed group were exposed to 95 dB noise, and the music-exposed group listened to Mozart's K. 448 music (65-75 dB) for 1 h daily over 7 days. An enzyme-linked immunosorbent assay was utilized to detect the levels of inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), in serum and tissues (lung, liver, and kidney). Western blot examined the phosphorylation levels of nuclear factor-κB (NF-κB) p65 in organ tissues.</p><p><strong>Results: </strong>Compared with the Control group, LPS-induced sepsis rats displayed a significant increase in the levels of TNF-α and IL-1β in serum, lung, liver, and kidney tissues, as well as a remarkable elevation in the p-NF-κB p65 protein expression in lung, liver, and kidney tissues. Noise exposure further amplified these inflammatory markers, while music exposure reduced them in LPS-induced sepsis rats.</p><p><strong>Conclusion: </strong>Noise exposure exacerbates inflammation by activating the NF-κB pathway, leading to the up-regulation of inflammatory markers during sepsis. On the contrary, music exposure inhibits NF-κB signaling, indicating a potential therapeutic effect in reducing inflammation.</p>","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"43 ","pages":"9603271241282584"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142143502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effects of short-time air pollution, SO2, and ozone on biochemical, histo-pathological, oxidative stress, and carcinogenesis related genes expressions in the liver of the rats.","authors":"Bita Sepehri, Roya Darbani, Mehran Mesgari-Abbasi, Sorayya Kheirouri, Dariush Shanehbandi, Monireh Khordadmehr, Mohammad Alizadeh","doi":"10.1177/09603271241263569","DOIUrl":"https://doi.org/10.1177/09603271241263569","url":null,"abstract":"<p><strong>Objective of the research: </strong>Air pollution is a universal issue and has significant deleterious effects on both human health and also environment. The important indicators of air pollution include ozone (O3), particulate matter (PM), nitrogen dioxide (NO2), and sulfur dioxide (SO2). This research aims to investigate the impacts of ambient air pollution (AAP), SO2, and O3 on oxidative stress parameters, liver tissue histopathology, and expression of some carcinogenesis-related genes in the hepatic tissue of rats.</p><p><strong>Materials and methods: </strong>32 Wistar rats were randomly allocated to four groups: the control group, the AAP group, the SO2 group (10 ppm), and the ozone group (0.6 ppm). Over a period of five consecutive weeks, the rats were exposed to the specified pollutants for 3 h daily; liver tissues were harvested and instantly fixed with formalin. Pathological changes were assessed in the tissue samples. Additionally, the RT-qPCR technique was utilized to investigate Expression alterations of BAX, p-53, BCL2, caspase-3, caspase-8 and caspase-9. Furthermore, 30 milligrams of hepatic tissues were extracted to assess the activities of oxidative stress enzymes.</p><p><strong>Results: </strong>The liver catalase and MDA activity were elevated in the air pollution (<i>p</i> < .05). Also, liver GPx activity in air pollution and ozone groups was significant in comparison to the control group (<i>p</i> < .05). The SO2 group exhibited severe lesions in histopathology examinations.</p><p><strong>Conclusions: </strong>The findings revealed an alteration in liver histopathology, an induction of oxidative stress, and the expression of some apoptosis-related genes in hepatic tissues after exposure to AAP, SO2, and O3.</p>","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"43 ","pages":"9603271241263569"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141790628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alkylating agents are possible inducers of glioblastoma and other brain tumors.","authors":"Carr J Smith, Thomas A Perfetti, Chirayu Chokshi, Chitra Venugopal, J Wesson Ashford, Sheila K Singh","doi":"10.1177/09603271241256598","DOIUrl":"10.1177/09603271241256598","url":null,"abstract":"<p><p>Epidemiological evidence of an association between exposure to chemical carcinogens and an increased risk for development of glioblastoma (GBM) is limited to weak statistical associations in cohorts of firefighters, farmers, residents exposed to air pollution, and soldiers exposed to toxic chemicals (e.g., military burn pits, oil-well fire smoke). A history of ionizing radiation therapy to the head or neck is associated with an increased risk of GBM. Ionizing radiation induces point mutations, frameshift mutations, double-strand breaks, and chromosomal insertions or deletions. Mutational profiles associated with chemical exposures overlap with the broad mutational patterns seen with ionizing radiation. Data on 16 agents (15 chemicals and radio frequency radiation) that induced tumors in the rodent brain were extracted from 602 Technical Reports on 2-years cancer bioassays found in the National Toxicology Program database. Ten of the 15 chemical agents that induce brain tumors are alkylating agents. Three of the 15 chemical agents have idiosyncratic structures and might be alkylating agents. Only two of the 15 chemical agents are definitively not alkylating agents. The rat model is thought to be of possible relevance to humans suggesting that exposure to alkylating chemicals should be considered in epidemiology studies on GBM and other brain tumors.</p>","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"43 ","pages":"9603271241256598"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140961364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}