Toxicology in Vitro最新文献_第8页

The protective mechanisms of glycyrrhizic acid for deoxynivalenol-induced toxicity in rabbit corneal stroma 甘草酸对脱氧雪腐镰刀醇致兔角膜基质毒性的保护机制。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-10-01 Epub Date: 2025-07-04 DOI: 10.1016/j.tiv.2025.106104

Chunlan Liang , Xuewei Xiong , Qi Shi , Qingqing Li , Guocheng Yu , Jingxiang Zhong , Lian Liu

{"title":"The protective mechanisms of glycyrrhizic acid for deoxynivalenol-induced toxicity in rabbit corneal stroma","authors":"Chunlan Liang , Xuewei Xiong , Qi Shi , Qingqing Li , Guocheng Yu , Jingxiang Zhong , Lian Liu","doi":"10.1016/j.tiv.2025.106104","DOIUrl":"10.1016/j.tiv.2025.106104","url":null,"abstract":"<div><h3>Objectives</h3><div>This study aimed to investigate the effects and mechanisms of deoxynivalenol (DON) on rabbit corneal stroma cell culture and observe the protective effect of glycyrrhizic acid (GA) against DON-induced damage.</div></div><div><h3>Methods</h3><div>Rabbit corneal stromal cells (RCSCs) were isolated and divided into groups: control group (CON), 0.5 mmol/L GA (GA group), 400 ng/mL DON (DON group), and 0.5 mmol/L GA + 400 ng/mL DON (GAD). The effect of GA on RCSCs induced by DON was evaluated using various assays, including CCK-8 assay, Flow cytometry, qPCR, and Western blot.</div></div><div><h3>Results</h3><div>DON inhibited RCSCs proliferation, increased apoptosis, and raised the proportion of cells in the S and G2/M phase. It raised reactive oxygen species (ROS) levels and reduced mitochondrial membrane potential (MMP). Additionally, DON upregulated Bax, Caspase-3, inflammatory factors (IL-1α, IL-1β, TNF-α), and matrix metalloproteinases (MMP-1/8), while downregulating tissue inhibitors of matrix metalloproteinases (TIMP-1) and type I collagen. In contrast, GA partially restored RCSCs proliferation and reduced apoptosis, inflammation, and collagen degradation.</div></div><div><h3>Conclusions</h3><div>DON can induce toxicity in RCSCs, promoting the expression of inflammatory factors, disrupting the balance between MMP-1/8 and TIMP-1, and promoting type I collagen degradation. Conversely, GA reduces the oxidative stress damage, cell apoptosis, and inflammatory reaction of RCSCs induced by DON, and reduces the degradation of type I collagen.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"108 ","pages":"Article 106104"},"PeriodicalIF":2.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144568074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transcriptomic dose-response by UVC and heavy ion radiation reveal pathways to immune impairment UVC和重离子辐射的转录组剂量反应揭示了免疫损伤的途径

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-10-01 Epub Date: 2025-05-24 DOI: 10.1016/j.tiv.2025.106086

Mingming Tian , Xiaolin Ding , Yue Pang , Dan Xu , Yeqing Sun , Pu Xia

{"title":"Transcriptomic dose-response by UVC and heavy ion radiation reveal pathways to immune impairment","authors":"Mingming Tian , Xiaolin Ding , Yue Pang , Dan Xu , Yeqing Sun , Pu Xia","doi":"10.1016/j.tiv.2025.106086","DOIUrl":"10.1016/j.tiv.2025.106086","url":null,"abstract":"<div><div>Irradiation-induced immune impairment has been linked to human immune diseases, such as myelodysplastic syndromes (MDS) and leukemia. Global molecular responses to genome instability in immune cells can be identified by using transcriptomics. However, it is hard to link the molecular mechanism to the disease outcomes in the previous mechanistic studies. Here, transcriptomic dose-responses in human CD4+ T lymphocytes exposed to ultraviolet and heavy ion radiation were revealed by identification of the gene expression patterns of differential expression genes (DEGs) and calculating the point of departure (POD) of each DEG and molecular pathway, which provided an opportunity for quantitively illustrating the biological process of irradiation-induced immune impairments. Two potential adverse outcome pathways (AOPs) to irradiation-related leukemia were identified by mapping the molecular pathways into the biological event cascades, which provided phenotypic anchoring for the toxicological mechanisms. In addition, this study also revealed that NOP14/ NOP14-AS1 could be potential biomarkers of irradiation-induced immune impairment. Our works strengthen the use of AOP network in the next-generation risk assessment of irradiation-related diseases.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"108 ","pages":"Article 106086"},"PeriodicalIF":2.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144147586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CiPA-qualified human iPSC-derived cardiomyocytes: A new frontier in toxicity testing by evaluating drug-induced arrhythmias cipa合格的人ipsc衍生心肌细胞：通过评估药物性心律失常进行毒性测试的新前沿。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-10-01 Epub Date: 2025-06-05 DOI: 10.1016/j.tiv.2025.106100

Vijay Bhaskar Reddy Konala , Rutuja Kuhikar , Shruti More , Matthias Gossmann , Bettina Lickiss , Peter Linder , Jaganmay Sarkar , Paresh Bhanushali , Amit Khanna

{"title":"CiPA-qualified human iPSC-derived cardiomyocytes: A new frontier in toxicity testing by evaluating drug-induced arrhythmias","authors":"Vijay Bhaskar Reddy Konala , Rutuja Kuhikar , Shruti More , Matthias Gossmann , Bettina Lickiss , Peter Linder , Jaganmay Sarkar , Paresh Bhanushali , Amit Khanna","doi":"10.1016/j.tiv.2025.106100","DOIUrl":"10.1016/j.tiv.2025.106100","url":null,"abstract":"<div><div>Drug-induced arrhythmias remain a significant challenge in drug development, often leading to serious cardiovascular complications and the withdrawal of approved drugs from the market. The Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative aims to enhance cardiac safety assessment by leveraging human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). In this study, we evaluated the effects of 28 drugs on a well-characterized hiPSC-CMs (YBLiCardio, Yashraj Biotechnology Ltd., Mumbai, India) using Electric Field Potential (EFP) measurements. The CardioExcyte 96 system recorded extracellular signals from 96 wells, functioning similarly to microelectrode arrays. Each drug was tested at four concentrations, and the effects were analyzed based on dynamic changes in beat patterns, with QT prolongation assessed by measuring the interval between the sodium spike and T-wave. Our results demonstrated that YBLiCardio cells responded to all drugs in line with the findings from the HESI CiPA study. Notably, droperidol (173 %) and domperidone (182 %), originally classified as intermediate-risk compounds, were identified as high-risk in our model, consistent with previous findings by Nguyen et al. (2017). Additionally, YBLiCardio showed enhanced predictive accuracy for chlorpromazine. These findings highlight the potential of hiPSC-CMs for proarrhythmia risk assessment within the CiPA framework, complementing ion channel data and in silico modeling approaches. Overall, YBLiCardio provides a robust and physiologically relevant platform for predicting cardiotoxicity, supporting safer and more efficient pre-clinical drug discovery & development.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"108 ","pages":"Article 106100"},"PeriodicalIF":2.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Corrigendum to “Integrative toxicity assessment of tocotrienol-rich fraction from palm oil using in silico methods and zebrafish embryotoxicity model” [Toxicology in Vitro, 107 (2025) 106062] “利用计算机方法和斑马鱼胚胎毒性模型对棕榈油中富含生育三烯醇的部分进行综合毒性评估”的勘误表[体外毒理学，107 (2025)106062]

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-10-01 Epub Date: 2025-06-12 DOI: 10.1016/j.tiv.2025.106099

Thenmoly Damodaran , Najib Sani Yahaya , Mohd Nizam Mordi

引用次数: 0

Molecular mechanistic approach to reveal decitabine's effect on DNMT gene modulation and its inhibitory role in heavy metal-induced proliferation in urinary bladder cancer cell line 地西他滨对重金属诱导的膀胱癌细胞DNMT基因调控及抑制作用的分子机制研究。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-10-01 Epub Date: 2025-05-23 DOI: 10.1016/j.tiv.2025.106082

Deepika Saini , Pankaj Kumar Chaudhary , Ganesh Kumar Verma , Jitendra Kumar Chaudhary , Raman Kumar , Sarama Saha , Partha Roy , Bela Goyal , Ramasare Prasad , Anissa Atif Mirza-Shariff

{"title":"Molecular mechanistic approach to reveal decitabine's effect on DNMT gene modulation and its inhibitory role in heavy metal-induced proliferation in urinary bladder cancer cell line","authors":"Deepika Saini , Pankaj Kumar Chaudhary , Ganesh Kumar Verma , Jitendra Kumar Chaudhary , Raman Kumar , Sarama Saha , Partha Roy , Bela Goyal , Ramasare Prasad , Anissa Atif Mirza-Shariff","doi":"10.1016/j.tiv.2025.106082","DOIUrl":"10.1016/j.tiv.2025.106082","url":null,"abstract":"<div><div>Heavy metals are pervasive environmental and occupational carcinogens known to induce uncontrolled cell proliferation. They influence a number of cellular processes, including proliferation, metabolism, apoptosis, and carcinogenesis. Among the several underlying mechanisms of carcinogenesis, metal-induced aberrant modulation of DNA methyltransferase (DNMT) activity may play crucial role. In this context, our study explored the proliferative and/or cytotoxic effects of heavy metals on the T24 urinary bladder cancer cell line. Additionally, we evaluated the effects of heavy metals and the chemotherapeutic agent decitabine on DNMT expression and activity. For investigative purposes, T24 cells were exposed to different heavy metals; namely, lead (Pb), chromium (Cr), cadmium (Cd), nickel (Ni), and arsenic (As) at concentrations ranging from 0.5 to 32 μM for 24, 48, and 72 h, as well as to decitabine (1 to 64 μM) for 72 h. Post-incubation, cell proliferation and migration increased, and mitochondrial membrane potential decreased significantly in the presence of heavy metals, especially Cr and Cd. Moreover, in the presence of Cr and Cd, expression of DNMT1 and DNMT3b genes enhanced significantly. Furthermore, decitabine treatment effectively inhibited Cd- and Cr-induced proliferation and downregulated expression of DNMT genes. In conclusion, heavy metals such as Cd and Cr may contribute to urinary bladder carcinogenesis through DNMT upregulation, while decitabine showedprotective effects by suppressing DNMT expression and inhibiting cell proliferation.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"108 ","pages":"Article 106082"},"PeriodicalIF":2.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Corrigendum to “Assessing the safety of midazolam: A comprehensive analysis of adverse events from FAERS” [Toxicology in vitro 105 (2025) 106023] “咪达唑仑的安全性评估：FAERS不良事件的综合分析”的更正[体外毒理学105 (2025)106023]

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-10-01 Epub Date: 2025-07-01 DOI: 10.1016/j.tiv.2025.106103

Jieyuan Chen , Zhaojun Wang , Li Wei , Songsong Mao

引用次数: 0

E171-induced toxicity in human iPSC-derived colon organoids: Effects on cell viability, ROS generation, DNA damage, and gene expression changes e171诱导的人类ipsc衍生的结肠类器官毒性：对细胞活力、ROS生成、DNA损伤和基因表达变化的影响

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-10-01 Epub Date: 2025-07-10 DOI: 10.1016/j.tiv.2025.106105

Nicolaj S. Bischoff , Anna K. Undas , Marcel van Herwijnen , Marcha Verheijen , Jacco J. Briedé , Simone G. van Breda , Dick T.H.M. Sijm , Theo M. de Kok

{"title":"E171-induced toxicity in human iPSC-derived colon organoids: Effects on cell viability, ROS generation, DNA damage, and gene expression changes","authors":"Nicolaj S. Bischoff , Anna K. Undas , Marcel van Herwijnen , Marcha Verheijen , Jacco J. Briedé , Simone G. van Breda , Dick T.H.M. Sijm , Theo M. de Kok","doi":"10.1016/j.tiv.2025.106105","DOIUrl":"10.1016/j.tiv.2025.106105","url":null,"abstract":"<div><div>Food-grade titanium dioxide (E171) is a widely used food additive with debated safety, particularly regarding its genotoxic effects. This study assessed the dose-dependent toxicity of E171 in human induced pluripotent stem cell (iPSC)-derived colon organoids. Organoids were exposed to E171 (0.1–1000 μg/mL) for 24 h, and effects on cell viability, reactive oxygen species (ROS) generation, DNA damage, and gene expression were evaluated.</div><div>Results showed no impact on cell viability but a dose-dependent increase in ROS formation, peaking at 1000 μg/mL. Electrospin Resonance Spectroscopy (ESR) showed a dose-dependent increase in ROS, with increased E171 concentrations. The alkaline comet assay revealed significant DNA damage from 100 μg/mL, with oxidative DNA damage detected at 10 μg/mL using formamidopyrimidine DNA glycosylase (FPG). RNA sequencing identified differentially expressed genes (DEGs) at 100 and 250 μg/mL, linked to translational activity, signal transduction, and DNA damage repair. Gene set enrichment analysis (GSEA) indicated activation of ribosome, chemical carcinogenesis–ROS, and metabolic pathways (carbon metabolism, glycolysis), while key regulatory pathways (Wnt, MAPK, PI3K-Akt) were suppressed.</div><div>These findings suggest that E171 induces oxidative stress and DNA damage, modulating transcriptomic pathways associated with metabolism, proliferation, and cancer. Further research is necessary to determine its long-term effects on human gastrointestinal health.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"108 ","pages":"Article 106105"},"PeriodicalIF":2.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144614228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effects of an environmental chemical mixture on early-stage embryo development: In vitro evidence from human embryonic stem cells 环境化学混合物对早期胚胎发育的影响：来自人类胚胎干细胞的体外证据。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-10-01 Epub Date: 2025-06-12 DOI: 10.1016/j.tiv.2025.106101

Bai Li , Yihang Kevin Pan , Xiaolei Jin , Hing Man Chan

{"title":"Effects of an environmental chemical mixture on early-stage embryo development: In vitro evidence from human embryonic stem cells","authors":"Bai Li , Yihang Kevin Pan , Xiaolei Jin , Hing Man Chan","doi":"10.1016/j.tiv.2025.106101","DOIUrl":"10.1016/j.tiv.2025.106101","url":null,"abstract":"<div><div>Environmental chemicals are known risk factors for adverse pregnancy outcomes. However, the effects of environmentally relevant concentrations of chemical mixtures are less studied. This study investigated the effects of a mixture containing 23 chemicals reported in blood samples of Nunavik pregnant women, termed the Nunavik Chemical Mixture (NCM), on embryo development using human embryonic stem cells (hESCs). hESCs were exposed to 0-100X of NCM (X is the sum of geometric mean concentrations of NCM's components) for 24 h and 6 d Cell viability, apoptosis, stress response, cell cycle, cytoskeleton, autophagy, and expression of lineage marker genes/proteins were measured after exposures. NCM decreased cell viability and adhesion, induced apoptosis, disrupted the cell cycle, and altered the expression of cytoskeleton, autophagy proteins, and lineage marker genes/proteins in a dose-dependent manner. These results suggested that NCM affected embryo development, leading to potential adverse pregnancy outcomes if it occurs <em>in vivo</em>. Moreover, the effects caused by NCM were different from those caused by the same doses of MeHg alone that we previously found, indicating potential interactions among components within the mixture. Our results highlight the importance of considering the potential combined effects of chemical mixtures when assessing health risks in populations exposed to various environmental chemicals.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"108 ","pages":"Article 106101"},"PeriodicalIF":2.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Detection of skin sensitization hazards in medical device materials using a combination of three alternative in vitro testing methods 使用三种可选的体外测试方法组合检测医疗器械材料中的皮肤致敏危害。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-10-01 Epub Date: 2025-05-21 DOI: 10.1016/j.tiv.2025.106084

Masayuki Okada, Harumi Tabata, Keiki Suzuki, Atsushi Kaneki

{"title":"Detection of skin sensitization hazards in medical device materials using a combination of three alternative in vitro testing methods","authors":"Masayuki Okada, Harumi Tabata, Keiki Suzuki, Atsushi Kaneki","doi":"10.1016/j.tiv.2025.106084","DOIUrl":"10.1016/j.tiv.2025.106084","url":null,"abstract":"<div><div>This study attempted to detect the skin sensitization hazards of medical device materials by combining multiple <em>in vitro</em> alternative testing methods. Nine materials were extracted using organic solvents, and the re-dissolved solutions were evaluated using the Amino acid Derivative Reactivity Assay (ADRA), Epidermal Sensitization Assay (EpiSensA), and human Cell Line Activation test (h-CLAT). The combined results of each test were compared with those of the Guinea Pig Maximization Test (GPMT) results. The findings of ADRA and h-CLAT were consistent with the GPMT results for seven of the nine materials, and EpiSensA was consistent with the GPMT results for eight of the nine materials. The findings of the “2 out of 3” and Sequential Testing Strategy (STS) approaches were compared with the GPMT results. The GMPT results for all nine materials were correctly predicted when the “2 out of 3” approach was used. When the STS was used, it correctly predicted the GMPT results for eight of the nine materials. Therefore, integrating the ADRA, EpiSensA, and h-CLAT may provide an effective testing method for detecting skin sensitization hazards of organic solvent extracts from medical device materials.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"108 ","pages":"Article 106084"},"PeriodicalIF":2.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development of a TK6-derived cell line expressing four human cytochrome P450s for genotoxicity testing 表达4种人类细胞色素p450的tk6衍生细胞系的建立及其遗传毒性试验

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-10-01 Epub Date: 2025-05-26 DOI: 10.1016/j.tiv.2025.106085

Xilin Li , Yuhan Wang , Hannah Xu , Xiaobo He , Si Chen , Xiaoqing Guo , Mugimane G. Manjanatha , Tong Zhou , Jessica Bonzo , Nan Mei

{"title":"Development of a TK6-derived cell line expressing four human cytochrome P450s for genotoxicity testing","authors":"Xilin Li , Yuhan Wang , Hannah Xu , Xiaobo He , Si Chen , Xiaoqing Guo , Mugimane G. Manjanatha , Tong Zhou , Jessica Bonzo , Nan Mei","doi":"10.1016/j.tiv.2025.106085","DOIUrl":"10.1016/j.tiv.2025.106085","url":null,"abstract":"<div><div>Metabolism is essential for <em>in vitro</em> genotoxicity testing. We previously developed a panel of TK6 cell lines, each expressing one of 14 human cytochrome P450 (CYP) enzymes, demonstrating their ability to effectively bioactivate indirect genotoxicants without relying on a rodent liver S9 fraction. In the present study, we extended this work by developing a TK6 cell line co-expressing four human CYP enzymes, including CYP2A6, CYP2E1, CYP2C19, and CYP3A4 (designated as TK6-4CYP), and subsequently assessed its capability to metabolize and activate pro-genotoxicants. Human lymphoblastoid TK6 cells were sequentially transduced with lentiviral vectors carrying CYP2A6/2E1 and CYP2C19/3A4, resulting in more than a 2<sup>10</sup>-fold increase in mRNA expression levels for each CYP compared to parental cells. RNA sequencing revealed selective upregulation of the four CYPs. Their protein expression and enzymatic activities were also confirmed. TK6-4CYP cells were subsequently tested with four CYP-metabolized pro-genotoxicants, including <em>N</em>-nitroso-diethylamine (NDEA) metabolized by CYP2A6, <em>N</em>-nitroso-dimethylamine (NDMA) by CYP2E1, <em>N</em>-nitroso-propranolol (NNP) by CYP2C19, and riddelliine by CYP3A4, in the micronucleus assay, cell cycle analysis, and comet assay. Significant increases were observed in the percentage (%) of micronuclei induction, G2/M phase arrest, and % DNA in tails with all compounds except riddelliine, which showed increases in % micronuclei induction and G2/M phase arrest but no positive response in the comet assay. This study establishes proof-of-concept for using a TK6 cell model co-expressing multiple drug-metabolizing enzymes for genotoxicity evaluation.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"108 ","pages":"Article 106085"},"PeriodicalIF":2.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144168141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0