REGULATORY TOXICOLOGY AND PHARMACOLOGY
·
2015
·
IF 2.031
Chenzhong Fei,Jie Zhang,Yang Lin,Xiaoyang Wang,Keyu Zhang,Lifang Zhang,Wenli Zheng,Mi Wang,Tao Li,Sui Xiao,Feiqun Xue,Chunmei Wang
Nitromezuril (NZL) is a novel triazine compound that exhibits remarkable anticoccidial activity. However, mutagenicity and genotoxicity of NZL have not been evaluated to date. This study evaluated the potential risks of NZL by testing for bacterial reverse mutation (Ames), mouse sperm abnormality (SA), bone marrow micronucleus (MN) and chromosomal aberration (CA). Mice were orally administered with NZL at 385, 192 and 96 mg/kg, corresponding to 0.5×, 0.25× and 0.125× the LD 50 of NZL, respectively. No significant increases in SA and CA were found in mice treated with NZL for 5 d and 3 d, respectively ( P > 0.05). NZL at 96–385 mg/kg did not have significant influence on micronucleated polychromatic erythrocyte counts ( P > 0.05). These results suggest that NZL is not genotoxic. However, Ames test results were positive both with and without the S9 system for Salmonella typhimurium TA98 and TA100, suggesting that NZL may be mutagenic. The mutagenic effects of NZL were different in in vitro and in vivo assays . Further studies should be conducted to confirm the safety of using and developing NZL as a novel anticoccidial drug.
研究领域:
毒理学
·
遗传学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Biobased Materials and Bioenergy
·
2017
·Vol. 11
·期 5
·505-509
·
IF 0.975
Pan Shaobing,Qiu Fengxian,Ping Zhang,Geng Rong,Xu Xueqin,Huang Tongxing,Ma Yichen,Yang Jiahui,Li Houzhi
Objectives: This paper focuses on comparing the micronucleus effect and evaluating genotoxicity of nano-zinc oxide and bulk-zinc oxide based on V. faba. root tip cells. Methods: The different concentration of nano-ZnO and bulk-ZnO suspensions are used as mutagens,
meanwhile, the paper calculates the micronucleus permillage of V. faba. root tip cells exposed by different treatment liquid. Results: 1. Both nano-ZnO and bulk-ZnO suspensions can induce higher micronucleus permillage. The micronucleus permillage induced by different concentration
of nano-ZnO and bulk-ZnO are all higher than the negative control group. The significance comparison of micronucleus permillage between bulk-ZnO and negative control group is significant (p < 0.05) and the significance comparison between nano-ZnO and negative control group is extremely
significant (p < 0.01), both of difference comparison have statistical significance. 2. The micronucleus permillage which is induced by nano-ZnO is higher than bulk-ZnO on the equal concentration. The significance comparison of them is extremely significant (p < 0.01),
the comparison has statistical significance. The genotoxicity to V. faba. root tip cells of nano-ZnO is higher than bulk-ZnO. 3. It has stronger operability and scientificalness that we use the optimized micronucleus test technique of V. faba. root tip cells to evaluate genotoxicity
of manufactured nanomaterials.
研究领域:
遗传学
·
毒理学
·
环境科学
✓ 已验证
DOI
高影响因子
JOURNAL OF APPLIED TOXICOLOGY
·
2020
·Vol. 41
·期 2
·265-275
·
IF 2.997
Zhonghan He,Yanfeng Li,Zhenwei Lian,Jin Liu,Hongyi Xian,Ran Jiang,Zuqing Hu,Daokui Fang,Dalin Hu
Accumulating evidence reveals that exosome plays an important role in cell-to-cell communication in both physiological and pathological processes by transferring bioactive molecules. However, the role of exosomal secretion in the adaption of its source cells to the stimuli of environmental chemicals remains elusive. In this study, we revealed that the exposure of hydroquinone (HQ; the main bioactive metabolite of benzene) to human bronchial epithelial cells (16HBE) resulted in decreased ability of cell proliferation and migration, and simultaneously DNA damage and micronuclei formation. Interestingly, when exosomal secretion of HQ treated 16HBE cells was inhibited with the inhibitor GW4869, cellular proliferation and migration were further significantly reduced; concurrently, their DNA damage and micronuclei formation were both further significantly aggravated. Herein, we conclude that exosomal secretion of 16HBE cells may be an important self-protective function against the toxic effects induced by HQ.
研究领域:
细胞生物学
·
毒理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2013
·
IF 3.01
Jianyong Li,Xiaojun Kong,Xiwang Li,Yajun Yang,Jiyu Zhang
Aspirin eugenol ester (AEE) is a promising drug candidate for treatment of inflammation, pain and fever and prevention of cardiovascular diseases with less side effects and it is important to characterize its genotoxicity. In this study, the genotoxicity of AEE was assessed with two standard genotoxicity assays of the Salmonella typhimurium mutagenicity assay (Ames test) and the mouse bone marrow micronucleus assay. In the Ames test , Salmonella strains TA97, TA98, TA100, TA102 and TA1535 were treated with or without the metabolic activation with a S9 fraction from Acroclor-induced rat liver. The doses of AEE were 5 mg/plate, 2.5 mg/plate, 1.25 mg/plate, 0.625 mg/plate and 0.3125 mg/plate, respectively. In the above tested strains, mutagenicity with or without the S-9 mixture was not detected. In the mammalian erythrocyte micronucleus assay, fifty mice were divided into five groups evenly and the AEE dose at 5000 mg/kg, 2500 mg/kg and 1250 mg/kg and the cyclophosphamide dose at 40 mg/kg as a positive control, the 0.5% of CMC-Na as negative control were administered. The results showed that AEE did not induce any significant increase in micronucleated erythrocytes after 24 h ( p < 0.01). Our results suggested that AEE was non-genotoxic in vivo or in vitro .
研究领域:
药理学
·
毒理学
·
遗传学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
·
2024
·
IF 4.7
Wenwen Luo,Keqi Hu,Yijing Chen,Lin Wang,Yungang Liu
Tris(2-butoxyethyl) phosphate (TBOEP) is an organophosphorus flame retardant ubiquitously present in the environment and even the human body. TBOEP is toxic in multiple tissues, which forms dealkylated and hydroxylated metabolites under incubation with human hepatic microsomes; however, the impact of TBOEP metabolism on its toxicity, particularly mutagenicity (typically requiring metabolic activation), is left unidentified. In this study, the mutagenicity of TBOEP in human hepatoma cell lines (HepG2 and C3A) and the role of specific CYPs were studied. Through molecular docking, TBOEP bound to human CYP1A1, 1B1, 2B6 and 3A4 with energies and conformations favorable for catalyzing reactions, while the conformations of its binding with human CYP1A2 and 2E1 appeared unfavorable. In C3A cells (endogenous CYPs being substantial), TBOEP exposing for 72 h (2-cell cycle) at low micromolar levels induced micronucleus, which was abolished by 1-aminobenzotriazole (inhibitor of CYPs); in HepG2 cells (CYPs being insufficient) TBOEP did not induce micronucleus, whose effect was however potentiated by pretreating the cells with PCB126 (CYP1A1 inducer) or rifampicin (CYP3A4 inducer). TBOEP induced micronucleus in Chinese hamster V79-derived cell lines genetically engineered for stably expressing human CYP1A1 and 3A4, but not in cells expressing the other CYPs. In C3A cells, TBOEP selectively induced centromere protein B-free micronucleus (visualized by immunofluorescence) and PIG-A gene mutations, and elevated γ-H2AX rather than p-H3 (by Western blot) which indicated specific double-strand DNA breaks. Therefore, this study suggests that TBOEP may induce DNA/chromosome breaks and gene mutations in human cells, which requires metabolic activation by CYPs, primarily CYP1A1 and 3A4.
研究领域:
毒理学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cell Death & Disease
·
2017
·Vol. 8
·期 8
·e2988
·
IF 5.965
Yan Siyuan,Liu Ling,Ren Fengxia,Gao Quan,Xu Shanshan,Hou Bolin,Wang Yange,Jiang Xuejun,Che Yongsheng
Deficiency of autophagy has been linked to increase in nuclear instability, but the role of autophagy in regulating the formation and elimination of micronuclei, a diagnostic marker for genomic instability, is limited in mammalian cells. Utilizing immunostaining and subcellular fractionation, we found that either LC3-II or the phosphorylated Ulk1 localized in nuclei, and immunoprecipitation results showed that both LC3 and Unc-51-like kinase 1 (Ulk1) interacted with γ -H2AX, a marker for the DNA double-strand breaks (DSB). Sunitinib, a multi-targeted receptor tyrosine kinase inhibitor, was found to enhance the autophagic flux concurring with increase in the frequency of micronuclei accrued upon inhibition of autophagy, and similar results were also obtained in the rasfonin-treated cells. Moreover, the punctate LC3 staining colocalized with micronuclei. Unexpectedly, deprivation of SQSTM1/p62 alone accumulated micronuclei, which was not further increased upon challenge with ST. Rad51 is a protein central to repairing DSB by homologous recombination and treatment with ST or rasfonin decreased its expression. In several cell lines, p62 appeared in the immunoprecipites of Rad51, whereas LC3, Ulk1 and p62 interacted with PARP-1, another protein involved in DNA repair and genomic stability. In addition, knockdown of either Rad51 or PARP-1 completely inhibited the ST-induced autophagic flux. Taken together, the data presented here demonstrated that both LC3-II and the phosphorylated Ulk1 localized in nuclei and interacted with the proteins essential for nuclear stability, thereby revealing a more intimate relationship between autophagy and genomic stability.
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
Foods
·
2024
·Vol. 13
·期 9
·1404
·
IF 4.7
Yuyang Yao,Juer Liu,Qiming Miao,Xinyue Zhu,Wei Hua,Na Zhang,Guangwei Huang,Xiangyang Lin,Shengquan Mi,Yanling Cheng,Roger Ruan
Almond hull, a substantial byproduct comprising more than half of almond fresh weight, has recently gained attention due to its functionality and sustainability benefits. Despite heightened interest, information regarding its toxicity remains limited. In order to assess its genotoxic potential, we conducted Good Laboratory Practice-compliant in vitro and in vivo studies following Organization for Economic Co-operation and Development (OECD) guidelines. No evidence of toxicity or mutagenicity was observed in a bacterial reverse mutation assay using five tester strains, evaluating almond hull at concentrations up to 5 mg/plate, with or without metabolic activation. Almond hull did not induce chromosome structural damage in a chromosome aberration assay using Chinese hamster ovary cells, nor did it cause any spermatogonial chromosomal aberration in tested male BALB/c mice. To evaluate its ability to induce DNA damage in rodents, a combined micronucleus assay was conducted in KM mice of both sexes. Almond hull was administered at doses of 1250, 2500, and 5000 mg/kg/day via gavage once daily for 2 days. No adverse effects of almond hull were observed in the micronucleus assay. Our results indicate no evidence of the genotoxic potential of almond hull administered up to the maximum concentrations of 5 g/kg, as recommended by OECD guidelines.
研究领域:
食品科学
·
毒理学
·
遗传学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
American Journal of Translational Research
·
2023
·
IF 2.2
Ting Xie,Xunshan Ren,Huangming Zhuang,Fuze Jiang,Yuelong Zhang,Panghu Zhou
Objective: Osteoarthritis (OA) is the most common degenerative joint disease leading to disability worldwide. Cellular senescence is considered to be a fundamental pathogenic mechanism in the development of OA and has attracted increasing attention. However, regulatory mechanisms underlying chondrocyte senescence in OA remain unclear. Methods: Bioinformatic methods were used to screen key genes. Immunohistochemistry and the quantitative reverse transcription polymerase chain reaction were used to evaluate gene expression. RNA intervention experiments were performed to explore the functions of key genes. Results: We used 494 aging-associated genes provided by the Aging Atlas to identify the co-expression modules associated with age and OA. Thirty age-associated differentially expressed genes (ASDEGs) were identified. Using cytoHubba in Cytoscape, we identified Jun as the hub-ASDEG for OA chondrocytes. We confirmed the downregulation of Jun in OA rats and senescent chondrocytes by immunohistochemistry and quantitative reverse transcription polymerase chain reaction, respectively. Inhibition of proliferation and accelerated senescence were observed in chondrocytes treated with siRNA against Jun. Mechanistically, we observed micronuclei formation and reduced expression of H3K9me3 and heterochromatin protein 1gamma in siRNA-Jun-treated chondrocytes, indicating that destabilization of chromatin occurred during this treatment. Conclusion: Jun plays a crucial role in OA development and causes senescence by destabilizing chromatin in chondrocytes. These findings provide new insights into OA progression and suggest promising therapeutic targets.
研究领域:
风湿病学
·
分子生物学
·
细胞生物学
·
老年学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2025
·
IF 14.1
Wei Duan,Rendy Hosea,Lingxian Wang,Cao Ruan,Fuqiang Zhao,Jingyi Liu,Hezhao Zhao,Makoto Miyagishi,Shourong Wu,Vivi Kasim
Immune checkpoint inhibitor (ICI) therapy is a promising anti-tumor therapeutic strategy; however, its efficacy in solid tumors is limited. Chromosome missegregation is common in various solid tumors; however, its role in tumor progression remains poorly understood, and its correlation with ICI is yet to be explored. Here, it is found that increased chromosome missegregation promotes tumor immune microenvironment, and eventually immunotherapeutic efficacy, by triggering pyroptosis. yin yang 2 (YY2) is identified as a mitotic checkpoint regulator, which promotes chromosome missegregation by upregulating BUB1B transcription. Increased chromosome missegregation promoted the formation of micronuclei and release of double-stranded DNA (dsDNA) into the cytosol, triggering an AIM2-mediated cytosolic dsDNA response. The subsequent pyroptosis strengthened the tumor immune microenvironment, thereby enhancing immunoinfiltration and cytotoxicity of CD8 + T cells, while preventing their exhaustion. Finally, through in vitro and in vivo experiments, it is demonstrated that combining YY2 overexpression-induced chromosome missegregation/cytosolic dsDNA response and PD-1 inhibitor significantly enhanced the efficacy of ICI immunotherapy in microsatellite instable and microsatellite stable colorectal cancer cells. Together, these findings provide new insights on the role of chromosome missegregation in triggering cytosolic dsDNA response-mediated pyroptosis and modulating the tumor immune microenvironment, suggesting a novel strategy for improving ICI therapeutic efficacy in colorectal cancer.
研究领域:
肿瘤学
·
免疫学
·
分子生物学
·
癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY
·
2021
·Vol. 40
·期 7
·1917-1925
·
IF 3.742
Hongyi Xian,Meilin Tang,Ying Chen,Zhenwei Lian,Yanfeng Li,Xiaowu Peng,Dalin Hu
The present study was conducted to assess the genotoxic potential of water from the Helong Reservoir, which was designated as a strategic drinking water source by the Guangdong Provincial Government of China in October 2016. Four kinds of common indigenous fish samples ( Labeo rohita , Cirrhinus molitorella , red tilapia, and Oreochromis niloticus ) were collected at 6 sampling sites during the period from July to November 2020. Fish from the clean drinking water source of the upper reaches of the Liuxihe Reservoir in Guangzhou were collected as the control. Both the alkaline single cell gel electrophoresis assay and the micronucleus test were used to detect DNA damage and the micronucleus rate in erythrocytes of fish samples, respectively. The results indicated that there was a significant increase in comet tail length, Olive tail moment, and micronucleus rates of all fish samples compared with those of the control ( p < 0.05). The order of sensitivity to DNA damage and micronucleus formation was Labeo rohita > Cirrhinus molitorella > red tilapia > Oreochromis niloticus . The results of the 2 kinds of experiments were in perfect agreement with each other. We conclude that there are obvious genotoxic effects from the water in the Helong Reservoir. As a strategic drinking water source, the safety of the Reservoir water quality should be considered. The local government should put the restoration of the Helong Reservoir water quality on the agenda as soon as possible. Environ Toxicol Chem 2021;40:1917–1925. © 2021 SETAC
研究领域:
环境科学
·
毒理学
·
水生生物学
·
水质管理
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2013
·
IF 3.01
Hui Dong,Demei Xu,Lihua Hu,Lingrui Li,Erqun Song,Yang Song
Tetrachlorobenzoquinone (TCBQ) is an active metabolite of pentachlorophenol (PCP). Although the genotoxic effect of PCP has been comprehensively investigated, there is little known about TCBQ’s genotoxic effects. In the current study, TCBQ was tested for its genotoxicity using HepG2 cells as experimental model. To select the exposure concentration of interest, cell viability was measured and three concentrations were used for further investigation. In single cell gel electrophoresis (SCGE) assay, concentration-dependent increase in tail length, tail DNA percentage and tail moment were detected following TCBQ exposure. Micronucleus (MN) assay indicated TCBQ gradually increased MN frequency and decreased nuclear division index (NDI). Enzyme-linked immunosorbent assay (ELISA) and western blotting analyses both showed TCBQ caused histone H2AX phosphorylation (γ-H2AX). Furthermore, the elevation of 8-hydroxydeoxyguanosine (8-OHdG) and reactive oxygen species (ROS) level indicated TCBQ-induced genotoxicity is associated with oxidative stress. On the other hand, N-acetyl-cysteine (NAC) administration significantly protected cells from the genotoxic effect of TCBQ. Overall, our data suggested TCBQ exerted genotoxic effect possibly via an oxidative damage mechanism in HepG2 cells and this toxicity is prevented by pretreatment with NAC.
研究领域:
毒理学
·
细胞生物学
·
遗传学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TOXICOLOGY LETTERS
·
2014
·
IF 3.355
Zhangjian Chen,Yun Wang,Te Ba,Yang Li,Ji Pu,Tian Chen,Yanshuang Song,Yongen Gu,Qin Qian,Jinglin Yang,Guang Jia
With the extensive application of titanium dioxide (TiO 2 ) nanoparticles (NPs) in food industry, there is a rising debate concerning the possible risk associated with exposure to TiO 2 NPs. The purpose of this study is to evaluate the genotoxicity of TiO 2 NPs using in vivo and in vitro test systems. In vivo study, the adult male Sprague-Dawley rats were exposed to anatase TiO 2 NPs (75 ± 15 nm) through intragastric administration at 0, 10, 50 and 200 mg/kg body weight every day for 30 days. The γ-H 2 AX assay showed TiO 2 NPs could induce DNA double strand breaks in bone marrow cells after oral administration. However, the micronucleus test revealed that the oral-exposed TiO 2 NPs did not cause damage to chromosomes or mitotic apparatus observably in rat bone marrow cells. In vitro study, Chinese hamster lung fibroblasts (V79 cells) were exposed to TiO 2 NPs at the dose of 0, 5, 10, 20, 50 and 100 μg/mL. Significant decreases in cell viability were detected in all the treated groups after 24 h and 48 h exposure. Significant DNA damage was only observed at the concentration of 100 μg/mL after 24 h treatment using the comet assay. The obvious gene mutation was observed at the concentration of 20 and 100 μg/mL after 2 h treatment using hypoxanthine-guanine phosphoribosyl transferase (HPRT) gene mutation assay. This study presented a comprehensive genotoxic evaluation of TiO 2 NPs, and TiO 2 NPs were shown to be genotoxic both in vivo and in vitro tests. The gene mutation and DNA strand breaks seem to be more sensitive genetic endpoints for the detection of TiO 2 NPs induced genotoxic effects.
研究领域:
毒理学
·
纳米技术
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）