Toxicology Research最新文献

{"title":"Biochemical Alterations and Motor Dysfunctions in Corpus Striatum of Rats Brain Exposed to Azo Dyes.","authors":"Pronit Biswas, Juli Jain, Whidul Hasan, Devasish Bose, Rajesh Singh Yadav","doi":"10.1093/toxres/tfae216","DOIUrl":"10.1093/toxres/tfae216","url":null,"abstract":"<p><p>Azo food dyes are prohibited in most countries, but their injudicious use is still reported particularly in the developing Nations. Continuous use of contaminated food raises health concerns and given this the present study designed to investigate the effects of 3 non-permitted azo dyes (metanil yellow - MY, malachite green - MG, and sudan III - SIII) on neurobehavioral, neurochemicals, mitochondrial dysfunction, oxidative stress, and histopathological changes in the corpus striatum of rats. Rats were grouped and treated with MY (430 mg/kg), MG (13.75 mg/kg), SIII (250 mg/kg) & mixture (YGR) (MY 143.33 + MG 4.52 + SIII 83.33 mg/kg) p.o. for 60 days showed a significant decrease in grip strength and motor activity, the activity of acetylcholinesterase (AChE), monoamine oxidase - B (MAO-B), and mitochondrial complex I and II compared to the control. The treated groups showed a significant increase in lipid peroxidation and a decrease in the level of reduced glutathione, superoxide dismutase, and catalase as compared to the control. Histopathology of the corpus striatum revealed immense damage. Data from the present study correlate between azo dyes and changes in the behavior of rats which have been associated with the altered biochemicals and neurochemicals activities. In conclusion, exposure to azo dyes caused neurotoxicity involving motor impairments associated with enhanced oxidative stress, mitochondrial dysfunctions, AChE and MAO-B inhibition, and neuronal damage in the corpus striatum of rats.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 6","pages":"tfae216"},"PeriodicalIF":2.2,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11652610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862615","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":"Microrna-342 inhibits hepatocellular carcinoma cell proliferation and promotes apoptosis through the FOXP1/MYCBP Signaling Axis.","authors":"Yanling Zhang, Guang Da Yang, Qian Ya Chen, Jinlong Zeng, Yang Cao","doi":"10.1093/toxres/tfae149","DOIUrl":"10.1093/toxres/tfae149","url":null,"abstract":"<p><p>To investigate the role and mechanism of miR-342 and FOXP1 on hepatocellular carcinoma cells. QRT-PCR was applied to determine the expression of miR-342, FOXP1 and MYCBP in normal hepatocyte cell lines (NHC), hepatocellular carcinoma cell lines (HEK-293 T) and human hepatocellular carcinoma cell lines (HepG2, MHCC97-L, Huh7 and SMMC7721). After knockdown or over-expression of miR-342 and FOXP1 in HepG2 cells respectively, cell proliferation and cell viability were measured using MTT assay and colony formation assay. Flow cytometry was adopted to test for apoptosis. Dual luciferase gene reporter assays were performed to validate the target relationship between FOXP1and miR-342 or MYCBP. The level of apoptosis-related proteins cleaved-caspase-3, Bcl-2 and Bax were measured by western blot. Compared with NHC, miR-342 expression was decreased and FOXP1 expression was up-regulated in hepatocellular carcinoma cell lines. MiR-342 could target and negatively regulate FOXP1. FOXP1 could promote the proliferation of hepatocellular carcinoma cells, positively regulate the expression of c-Caspase-3, Bax, negatively regulate Bcl-2 and inhibit apoptosis. FOXP1 can also target and positively regulate MYCBP. The expression of MYCBP was up-regulated in the hepatocellular carcinoma cell lines, while overexpression of miR-342 decreased MYCBP expression promoted by overexpression of FOXP1. MiR-342 can inhibit FOXP1/MYCBP signaling axis to regulate the members of Caspase-3 and Bcl-2 family to inhibit the proliferation and promote apoptosis of hepatocellular carcinoma cells.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 6","pages":"tfae149"},"PeriodicalIF":2.2,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11649998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142851789","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":"Cyclophosphamide-induced multiple organ dysfunctions: unravelling of dose dependent toxic impact on biochemistry and histology.","authors":"Asim Amitabh Sahu, Ankita Mukherjee, Satendra Kumar Nirala, Monika Bhadauria","doi":"10.1093/toxres/tfae201","DOIUrl":"10.1093/toxres/tfae201","url":null,"abstract":"<p><strong>Background: </strong>Cyclophosphamide, an immunosuppressive alkylating agent, has been used against breast cancer, lymphoma and myeloid leukemia. Despite various therapeutic uses, its toxic impacts on multiple organs remains to be fully elucidated.</p><p><strong>Aim: </strong>This study aimed to investigate dose dependent toxic impact of cyclophosphamide on liver, kidney, brain and testis emphasizing serum and tissue biochemical and histological alterations.</p><p><strong>Materials and methods: </strong>Experimental design consisted of five groups of albino rats. Group 1-5 were administered vehicle for five consecutive days. On 6^th day, group 1 received vehicle only and termed as control; group 2-5 received cyclophosphamide through intraperitoneal route at the rate of 50, 100, 150 and 200 mg/kg dose, respectively. After 24 h of the last administration, rats were euthanised; serum and tissue biochemistry; histology, sperm count and its motility were performed.</p><p><strong>Results: </strong>Serological, biochemical and histological indices exhibited dose dependent deviations from their regular status as a marker of toxicity in liver, kidney, brain and testis. Tukey's HSD post hoc test revealed maximum damage in multiple organs with 200 mg/kg dose of cyclophosphamide.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 6","pages":"tfae201"},"PeriodicalIF":2.2,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11650506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142851702","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":"Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as mortality predictors in acute Aluminum phosphide (grain pills) poisoning: clinical insights and risk assessment.","authors":"Asmaa F Sharif, Heba A Mabrouk, Sanaa A Abdo, Abdelhamid Mohamed Elwy, Manar M Fayed","doi":"10.1093/toxres/tfae212","DOIUrl":"10.1093/toxres/tfae212","url":null,"abstract":"<p><strong>Background: </strong>Aluminum phosphides (AlP) is a solid fumigant pesticide known for its high toxicity and mortality. Diagnosis of AlP is based on the history and clinical examination. The literature on the early prediction of adverse outcomes following AlP exposure is limited. Therefore, the current study aimed to investigate the role of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte Ratio (PLR) as early accessible predictors of mortality in AlP-exposed patients.</p><p><strong>Method: </strong>We conducted a retrospective cross-sectional study on 420 adult patients with acute AlP poisoning.</p><p><strong>Results: </strong>This study reported mean NLR and PLR of 4.07 ± 3.82 and 182.97 ± 147.29, respectively. Patients with high NLR and PLR showed more severe presentation, indicated by the significantly lower Glasgow scales and higher poison severity score grades. Besides, the need for mechanical ventilation, vasopressor therapy, and ICU admission was significantly higher among patients with high NLR and PLR (<i>P</i> = 0.000). We observed a significantly higher proportion of mortality among patients with high NLR (69.5%) and PLR (87.4%) (<i>P</i> = 0.000). The NLR > 3.42, PLR > 172.5, and their combinations were significant predictors of mortality, showing area under curves above 0.94. Utilizing a combination of NLR and PLR yielded a modestly improved performance as a mortality predictor with a slight increase in the Youden index (0.81). The high NLR and high PLR groups had mean survival times of 28.851 and 16.256 h respectively.</p><p><strong>Conclusion: </strong>These findings suggest that high NLR and PLR are associated with a worse prognosis and a higher mortality risk among patients with acute AlP poisoning.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 6","pages":"tfae212"},"PeriodicalIF":2.2,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11646068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826785","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 carcinogenic and non-carcinogenic health risks, and cytogenotoxicity of wastewaters from natural and artificial fishponds indiscriminately disposed in Nigeria.","authors":"Okunola Adenrele Alabi, Olufemi M Ashamo, Rhema Adedamola Akinyanju, Florence Yosola Faleye, Tomiwa Amos Afolabi, Funmilayo Esther Ayeni, Yetunde Mercy Adeoluwa","doi":"10.1093/toxres/tfae213","DOIUrl":"10.1093/toxres/tfae213","url":null,"abstract":"<p><p>As the demand for fish increases, the amount of wastewater generated from fishponds is also increasing with potential environmental and public health effects from their indiscriminate disposal. This study aimed at comparative analyses of the physicochemical and heavy metal constituents and potential DNA damage by wastewaters from natural and artificial fishponds using <i>Allium cepa</i> assay. <i>A. cepa</i> were grown on 3.13, 6.25, 12.5, 25.0, and 50.0% (v/v; wastewater/tap water) concentrations of each wastewater. At 48 and 72 h, respectively, genotoxic and root growth inhibition analyses were carried out on the exposed onions. The onion root tips exposed to wastewaters showed a significant (<i>P</i> < 0.05) inhibition of root growth and cell division in a concentration-dependent manner. Additionally, chromosomal abnormalities like spindle disturbances, sticky chromosomes, micronucleus, bridges, and binucleated cells were observed in the exposed onions and their induction was higher significantly relative to the negative control. Generally, wastewater from the natural fishpond caused higher chromosomal aberrations than the wastewater from artificial fishpond. It is our belief that the cytotoxicity and genotoxicity observed in the onions were primarily caused by heavy metals like Cr, Cd, Fe, Pb, Cu, and Zn found in the wastewaters. These metals also showed a significant carcinogenic and non-carcinogenic risks in children and adults with Cd as the highest contributor to these detrimental risks. Ingestion route was the major exposure route to the toxic metals in these wastewaters. Wastewater from the natural fishpond showed a higher health risk than the wastewater from the artificial fishpond. These findings suggest that the wastewaters from natural and artificial fishpond contain compounds that might induce cytogenotoxicity in exposed organisms.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 6","pages":"tfae213"},"PeriodicalIF":2.2,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11646070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826755","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":"In vitro effect of vitaminB₁₂ on embyro growth by induction of hypoxia in culture.","authors":"Dilara Patat, Mehtap Nisari, Harun Ulger, Tolga Ertekin, Ertugrul Dagli, Dicle Cayan, Ozge Al, Hatice Guler, Goksemin Fatma Sengul, Mustafa Tastan","doi":"10.1093/toxres/tfae207","DOIUrl":"10.1093/toxres/tfae207","url":null,"abstract":"<p><p>In this study, effects of vitaminB₁₂ on embryonic development have been investigated by supplying vitaminB₁₂ on a hypoxia-induced embryo culture. 9.5-day-old embryos from Wistar albino adult pregnant rats were used in our experimental set up.10 μM and 100 μM vitaminB₁₂ were added to culture medium which is then exposed to in vitro hypoxia. Additionally, 11.5-day-old embryos and yolksacs were examined morphologically. Different vitaminB₁₂ doses are compared within experimental groups. It was found that both control and experimental groups in 11.5-day-old embryos are at same developmental stage. It was also determined that oxygen deficiency influenced embryonic development and yolk sac vascularity in hypoxia group, are lagging behind in all experimental groups (<i>P</i> < 0.05). However, the development of vitaminB₁₂ embryos were similar to control group under normoxic conditions (<i>P</i> > 0.05). It was also observed that development was compensated through supplement of vitaminB₁₂ to hypoxia group <i>(P < 0.05</i>). It was indicated that the development in H + 100 μM vitB₁₂ groups was quite close to control group. However, development of H + 10 μM vitB₁₂ embryos were in parallel with hypoxic group. Furthermore, H + 100 μM vitB₁₂ group showed higher embryonic development than H + 10 μM vitB₁₂ group (<i>P</i> < 0.05).VitaminB₁₂ treatment has been used to prevent intrauterine growth restriction which can be caused by many different pharmacological agents. However, nobody has investigated effects of vitaminB₁₂ on hypoxia-induced early embryo growth retardation. In the light of our findings, administration of 100 μM vitaminB₁₂ restores damage of embryonic development due to hypoxia and this application also increases embryonic vascularity and circulation. Thus, supplementation of vitaminB₁₂ can be offered as a therapeutic approach towards cell death and diseases such as neurovascular and cardiovascular diseases and in the near future.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 6","pages":"tfae207"},"PeriodicalIF":2.2,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811577","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":"SARM1 in the pathogenesis of immune-related disease.","authors":"Yihan Ye, Fuyong Song","doi":"10.1093/toxres/tfae208","DOIUrl":"10.1093/toxres/tfae208","url":null,"abstract":"<p><strong>Background: </strong>Sterile alpha and toll interleukin receptor motif-containing protein 1 (SARM1) are primarily expressed in the mammalian nervous system, with their presence in neurons being associated with mitochondrial aggregation. SARM1 functions as a mediator of cell death and morphological changes, while also regulating Waller degeneration in nerve fibers and influencing glial cell formation.</p><p><strong>Purpose: </strong>Recent reports demonstrate SARM1 serves as a connector in the Toll-like receptor (TLR) pathway and plays a role in regulating inflammation during periods of stress such as infection, trauma, and hypoxia. These findings offer new insights into pathogenesis research and the prevention and treatment of neurodegenerative diseases and pathogen infections.</p><p><strong>Methods: </strong>This review synthesizes recent findings on the immune-related mechanisms of SARM1, emphasizing its roles in inflammation and its functional impact on the nervous system and other bodily systems.</p><p><strong>Conclusions: </strong>Understanding the multifaceted roles of SARM1 in immune regulation and neuronal health provides novel insights into its involvement in disease pathogenesis. These insights hold promise for advancing research into the prevention and treatment of neurodegenerative diseases and pathogen-induced conditions.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 6","pages":"tfae208"},"PeriodicalIF":2.2,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811591","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":"Cancer-associated fibroblasts affect breast cancer cell sensitivity to chemotherapeutic agents by regulating NRBP2.","authors":"Xiaoyan Jin, Yong Chen, Gui Wang","doi":"10.1093/toxres/tfae204","DOIUrl":"10.1093/toxres/tfae204","url":null,"abstract":"<p><strong>Objective: </strong>To uncover the role of nuclear receptor-binding protein 2 (NRBP2) in cancer-associated fibroblasts (CAFs), and CAFmediated TAM sensitivity in breast cancer (BC).</p><p><strong>Methods: </strong>10 pairs of matched tumor tissues and adjacent normal tissues were collected and CAFs and normal fibroblasts (NFs) were isolated. CCK-8 as well as colony formation assays showed the effects on cell growth. qPCR and Immunoblot showed the expression of NRBP2 in CAFs. FCM as well as Immunoblot assays exhibited the effects on cell apoptosis. Immunoblot further confirmed the mechanism.</p><p><strong>Results: </strong>CAFs contributed to BC cell growth. In addition, the expression of NRBP2 is downregulated in CAFs. NRBP2 suppressed CAF-induced resistance in BC cells. Further, NRBP2 expression in CAF group increased TAM induced apoptosis. Mechanically, NRBP2 in CAFs inhibited Akt pathway, therefore suppressed resistance in BC cells.</p><p><strong>Conclusion: </strong>CAFs affected BC cell sensitivity to TAM by regulating NRBP2.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 6","pages":"tfae204"},"PeriodicalIF":2.2,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811512","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":"Ferulic acid improves palmitate-induced insulin resistance by regulating IRS-1/Akt and AMPK pathways in L6 skeletal muscle cells.","authors":"Jae Eun Park, Ji Sook Han","doi":"10.1093/toxres/tfae197","DOIUrl":"10.1093/toxres/tfae197","url":null,"abstract":"<p><strong>Objective: </strong>Increased plasma-free fatty acid (FFA) induced by obesity can trigger insulin resistance and it is a significantly dangerous constituent in the progression of diabetes. Although ferulic acid has various physiological functions, no studies have examined ferulic acid's effects on insulin-resistant muscle cells. This study investigated the effect of ferulic acid on improving palmitic acid-induced insulin resistance in L6 skeletal muscle cells.</p><p><strong>Methods: </strong>Palmitic acid induces insulin resistance by inhibiting the phosphorylation of IRS-1_tyr and stimulating the phosphorylation of IRS-1_ser in diabetes. Thus, palmitic acid (0.75 mM) was used as an insulin resistance inducer and ferulic acid was treated at various concentrations (2, 5, 10, and 20 uM) in L6 skeletal muscle cells.</p><p><strong>Results: </strong>Palmitic acid significantly reduced the cell viability of L6 skeletal muscle cells, whereas ferulic acid treatment significantly increased cell viability in a concentration-dependent manner. Palmitic acid significantly reduced glucose uptake due to insulin resistance in the muscle cells; however, ferulic acid treatment remarkably increased glucose uptake. Ferulic acid promoted the phosphorylation of IRS-1_tyr that palmitic acid inhibited, while also suppressing the palmitic acid-induced phosphorylation of IRS-1_ser. Ferulic acid activated PI3K and then stimulated the phosphorylation of Akt, which increased PM-GLUT4 expression, thereby stimulating glucose uptake into insulin-resistant muscle cells. Ferulic acid also increased glycogen synthesis by phosphorylating GSK3β via the Akt pathway. Additionally, ferulic acid significantly promoted phosphorylation of AMPK, enhancing PM-GLUT4 levels and glucose uptake.</p><p><strong>Conclusions: </strong>These results suggest that ferulic acid may improve palmitate-induced insulin resistance by regulating IRS-1/ Akt and the AMPK pathway in L6 skeletal muscle cells.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 6","pages":"tfae197"},"PeriodicalIF":2.2,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811519","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":"Optimization of concentrations and exposure durations of commonly used positive controls in the in vitro alkaline comet assay.","authors":"Seda İpek Tekneci, Aylin Üstündağ, Yalçın Duydu","doi":"10.1093/toxres/tfae195","DOIUrl":"10.1093/toxres/tfae195","url":null,"abstract":"<p><p>Endogenous and exogenous factors cause DNA damage through chemical changes in the genomic DNA structure. The comet assay is a versatile, rapid, and sensitive method for evaluating DNA integrity at the individual cell level. It is used in human biomonitoring studies, the identification of DNA lesions, and the measurement of DNA repair capacity. Despite its widespread application, variations between studies remain problematic, often due to the lack of a common protocol and appropriate test controls. Using positive controls is essential to assess inter-experimental variability and ensure reliable results. Hydrogen peroxide (H₂O₂) is the most commonly used positive control, while potassium bromate (KBrO₃), methyl methanesulfonate (MMS), ethyl methanesulfonate (EMS), <i>N</i>-ethyl-<i>N</i>-nitrosourea (ENU), and etoposide are used less frequently. However, differences in concentrations and exposure durations prevent the confirmation of test method efficacy. This study investigates the dose-response relationship for H₂O₂, KBrO₃, MMS, EMS, ENU and etoposide in the comet assay for 30 and 60-minute exposure durations in 3T3 cell lines. Accordingly recommended concentrations and exposure durations were found to be 50 μM 30 minutes (H₂O₂); 500 μM 60 min. (MMS); 10 μM 30 min. (Etoposide); 0.2 mM 30 min. and 2 mM 60 min. (EMS); 2 mM 30 min. (ENU); 500 μM 30 min. and 50 μM 60 min. (KBrO₃). Our findings will contribute to reducing inter-laboratory variability by offering guidance on selecting doses and exposure durations for positive controls in the <i>in vitro</i> alkaline comet assay.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 6","pages":"tfae195"},"PeriodicalIF":2.2,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805656","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}