JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
·
2019
·Vol. 99
·期 7
·3548-3554
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IF 2.422
Wen Nie,Kezhou Cai,Yuzhu Li,Zehui Tu,Bing Hu,Cunliu Zhou,Conggui Chen,Shaotong Jiang
BACKGROUND The characteristics of carcinogenic polycyclic aromatic hydrocarbons (PAHs) produced from various fatty acids, as important components of fats and oils, at high temperature are still little known. The reason is because the existing data are from experiments conducted in complex food systems. In this study, 12 PAHs produced from nine fatty acids, representing saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs), were investigated in a model system heated at 98, 165 and 240 °C. RESULTS SFAs can with difficulty be pyrolyzed to generate PAHs at 98 °C, but small amounts of PAHs were determined in MUFAs (44.97 µg kg −1 ) and PUFAs (177.73 µg kg −1 ). When the temperature reached 165 °C, there were totals of 27.59, 142.8 and 449.68 µg kg −1 PAHs assayed in SFAs, MUFAs and PUFAs, respectively. The amounts of PAHs generated from SFAs, MUFAs and PUFAs at 240 °C were higher when compared with those of the 165 °C group ( P < 0.05). With an increase of heating temperature, the proportion of PAHs with four to five rings increased. Under the same heating conditions, the concentration of PAHs in fatty acids increased with an increase in the number of double bonds. CONCLUSIONS More PAHs, especially carcinogenic ones with four to five rings, will be produced in fatty acids heated at higher temperature. The content of PAHs generated from fatty acids increased with an increase in the number of double bonds. This study will increase the understanding of the production characteristics of PAHs from various fatty acids under heating condition. © 2019 Society of Chemical Industry
研究领域:
食品科学
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毒理学
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化学
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DOI
PubMed
高影响因子
MOLECULAR CARCINOGENESIS
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2024
·
IF 3
Junyi Jin,Yihui Wang,Yaoyuan Hu
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. STAM binding protein-like 1 (STAMBPL1), a key member of the COP9 signalosome subunit 5/serine protease 27/proteasome 26S subunit non-ATPase 7 (JAMM) family, is closely associated with tumor development. In this work, data from GSE101728 and GSE84402 chips were analyzed, and STAMBPL1 was selected as the target factor. This study aimed to reveal the potential function of STAMBPL1 in HCC. Clinical results showed that STAMBPL1 was significantly increased in tumor tissues of HCC patients, and its expression was strongly associated with tumor size and TNM stage. Furthermore, STAMBPL1-overexpressed Hep3B2.1-7 cell line or STAMBPL1-silenced SNU-182 cell line were established using lentivirus carrying cDNA encoding STAMBPL1 mRNA or shRNA targeting STAMBPL1, respectively. STAMBPL1-overexpressed cells exhibited a pronounced enhancement of proliferation in vitro and in vivo. Exogenous expression of STAMBPL1 increased the percentage of cells in the S phase and upregulated the expressions of CyclinD1 and Survivin. As expected, STAMBPL1 knockdown exhibited completely opposite effects, resulting in impaired tumorigenicity in vitro and in vivo. Mechanistically, STAMBPL1 activated Wnt/β-catenin pathway and increased the expression of downstream cancer-promoting genes. Interestingly, we found that STAMBPL1 was transcriptionally regulated by sterol regulatory element-binding protein 1 (SREBP1), a modulator of lipid metabolism, as evidenced by luciferase reporter and chromatin-immunoprecipitation (Ch-IP) assays. Notably, STAMBPL1 overexpression increased lipid accumulation in HCC cells and xenograft tumors. Totally our findings suggest that STAMBPL1 plays a vital role in the tumorigenicity of HCC cells. Modulation of Wnt/β-catenin and lipid metabolism may contribute to its pro-cancer effects. STAMBPL1 may serve as a therapeutic target of HCC.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2018
·
IF 3.412
Yukun Feng,Saide Wang,Hui Wang,Ying Peng,Jiang Zheng
Methyleugenol (ME), a natural ingredient of several herbs and spices used in the human diet, is hepatocarcinogenic in rodents. Following metabolic activation to the reactive carbocation intermediate, ME can bind covalently to DNA, which is directly associated with its carcinogenicity. In this work, a non-invasive approach to determine ME exposure was established by monitoring the urinary N6-(methylisoeugenol-3′-yl)-2′-deoxyadenosine (ME-dA) adduct. The developed method entails liquid–liquid extraction enrichment of urinary ME-dA, incorporation of deuterated ME-dA as an internal standard, and analysis by liquid chromatography coupled tandem mass spectrometry. Male rats (10–12 weeks, 180–200 g) were treated (p.o.) with ME, and ME-dA was excreted in urine in a dose- and time-dependent manner. The non-invasive approach enabled us to successfully determine exposure to ME-containing herbs and spices. These results suggest that ME-dA can potentially serve as an effective biomarker of ME exposure in rats. It is expected that the developed approach of detecting urinary ME-dA will facilitate the investigation of ME carcinogenesis.
研究领域:
毒理学
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分析化学
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癌症研究
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产品关联
DOI
PubMed
高影响因子
Environmental Science-Nano
·
2024
·Vol. 11
·期 5
·1817-1846
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IF 5.8
Yiqun Mo,Yue Zhang,Qunwei Zhang
With the exponential growth of the nanotechnology field, the global nanotechnology market is on an upward track with fast-growing jobs. Nickel (Ni)-containing nanoparticles (NPs), an important class of transition metal nanoparticles, have been extensively used in industrial and biomedical fields due to their unique nanostructural, physical, and chemical properties. Millions of people have been/are going to be exposed to Ni-containing NPs in occupational and non-occupational settings. Therefore, there are increasing concerns over the hazardous effects of Ni-containing NPs on health and the environment. The respiratory tract is a major portal of entry for Ni-containing NPs; thus, the adverse effects of Ni-containing NPs on the respiratory system, especially the lungs, have been a focus of scientific study. This review summarized previous studies, published before December 1, 2023, on the cytotoxic, genotoxic, and carcinogenic effects of Ni-containing NPs on humans, lung cells in vitro, and rodent lungs in vivo, and the potential underlying mechanisms were also included. In addition, whether these adverse effects were induced by NPs themselves or Ni ions released from the NPs was also discussed. The extra-pulmonary effects of Ni-containing NPs were briefly mentioned. This review will provide us with a comprehensive view of the pulmonary effects of Ni-containing NPs and their underlying mechanisms, which will shed light on our future studies, including the urgency and necessity to produce engineered Ni-containing NPs with controlled and reduced toxicity, and also provide a scientific basis for developing nanoparticle exposure limits and policies.
研究领域:
毒理学
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环境健康
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纳米医学
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产品关联
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
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2021
·
IF 6.558
Kai Nan,Man He,Beibei Chen,Bin Hu
For a deep understanding of arsenic's mutagenicity , carcinogenicity and teratogenicity , the elucidation of arsenic binding proteins in organisms is a necessary prerequisite. Herein, a biotinylated phenylarsenite (Bio-PAO(III)) probe was synthesized for in situ binding to arsenic binding proteins in HepG2 cells. The Bio-PAO(III)-arsenic binding proteins complexes were captured by the prepared streptavidin-magnetic beads (SA-MBs) by specific interaction of biotin-SA. After magnetic separation, the arsenic binding proteins in the eluent was separated by sodium dodecyl sulfate-polyacrylamide - gel electrophoresis , and the in-gel tryptic digested protein bands were subjected to capillary high performance liquid chromatography coupled with electrospray ionization mass spectrometry analysis. 32 kinds of arsenic binding proteins were identified in HepG2 cells, which could be divided into three groups, structure proteins, enzymes related with tricarboxylic acid cycle and fatty synthesis and transcriptional regulator. Poly [ADP-ribose] polymerase 1 and general transcription factor IIH subunit 1 were identified to bind with arsenicals, which may affect the process of nucleotide excision repair in HepG2 cells.
研究领域:
毒理学
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蛋白质组学
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分子生物学
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DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
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2024
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IF 8.2
Zhourui Xu,Jianjian Wei,Aroob Abid,Zirui Liu,Yasen Wu,Jia Gu,Dehua Ma,Min Zheng
Halobenzoquinones (HBQs) are a class of disinfection byproducts with high cytotoxicity and potential carcinogenicity , which have been widely detected in chlorination of drinking water and swimming pool water. However, to date, the formation of HBQs upon ozonation and the HBQ precursors have been overlooked. This study investigated the formation of chlorinated and dechlorinated HBQs from six dichlorophenol (DCP) isomers. The monomeric and dimeric HBQs were identified in all the ozonation effluents, exhibiting 1–100 times higher toxicity levels than their precursors. The sum of detected HBQs intensity had a satisfactory linear relation with the maximum toxic unit ( R 2 = 0.9657), indicating the primary toxicity contribution to the increased overall toxicity of effluents. Based on density functional theory calculations, when ozone attacks the para carbon to the hydroxyl group of 2,3-DCP, the probability of producing chlorinated HBQs is 80.41 %, indicating that the para carbon attack mainly resulted in the formation of monomeric HBQs. 2,3-dichlorophenoxy radicals were successfully detected in ozonated 2,3-DCP effluent through electron paramagnetic resonance and further validated using theoretical calculation, revealing the formation pathway of dimeric HBQs. The results indicate that chlorinated phenols, regardless of the positions of chlorine substitution, can potentially serve as precursors for both chlorinated and dechlorinated HBQs formation during ozonation.
研究领域:
环境科学
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毒理学
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水处理工程
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DOI
PubMed
高影响因子
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
·
2021
·Vol. 105
·期 13
·5607-5616
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IF 4.813
He Ying,Ding Haotian,Xia Xingya,Qi Wenyi,Wang Huaisong,Liu Wenyuan,Zheng Feng
Abstract Nitrosamine compounds, represented by N -nitrosodimethylamine, are regarded as potentially genotoxic impurities (PGIs) due to their hazard warning structure, which has attracted great attention of pharmaceutical companies and regulatory authorities. At present, great research gaps exist in genotoxicity assessment and carcinogenicity comparison of nitrosamine compounds. In this work, a collection of GFP-fused yeast cells representing DNA damage repair pathways were used to evaluate the genotoxicity of eight nitrosamine compounds (10 −6 –10 5 μg/mL). The high-resolution expression profiles of GFP-fused protein revealed the details of the DNA damage repair of nitrosamines. Studies have shown that nitrosamine compounds can cause extensive DNA damage and activate multiple repair pathways. The evaluation criteria based on the total expression level of protein show a good correlation with the mammalian carcinogenicity data TD 50 , and the yeast cell collection can be used as a potential reliable criterion for evaluating the carcinogenicity of compounds. The assay based on DNA damage pathway integration has high sensitivity and can be used as a supplementary method for the evaluation of trace PGIs in actual production. Key points • The genotoxicity mechanism of nitrosamines was systematically studied . • The influence of compound structure on the efficacy of genotoxicity was explored . • GFP-fused yeast cells have the potential to evaluate impurities in production . Graphical abstract
研究领域:
毒理学
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分子生物学
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药学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF FLUORESCENCE
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2025
·
IF 3.1
Zhang Hongmei,Yang Yunxia,Wang Yanqing
Sudan dyes are recognized as carcinogens, which are strictly determined whether there are them in food for food safety. Hence, in order to understand the mechanism at the molecular level, this work investigated the binding interactions of Sudan I-IV with calfthy mus DNA. The synchronous fluorescence and UV–vis spectral results suggested the complex formation between Sudan I-IV and ct-DNA. EB and Hoechst 33258 displacement experimental results confirmed the binding sites of Sudan I-IV in ct-DNA and the minor groove-binding mode of Sudan I-IV with ct-DNA. The molecular modeling computational method also proved binding mode, which is consistent with the spectral experiments. In addition, the aromatic rings of Sudan I-IV play important roles in binding with DNA. Compared to Sudan I and II, the increase of molecular conjugation system enhances the binding abilities of Sudan III and Sudan IV with DNA. Vdm + Hbond + desolv energies of them are the main contribution of their combined energies.
研究领域:
生物化学
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食品安全
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分子生物学
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DOI
PubMed
高影响因子
ONCOGENE
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2020
·Vol. 39
·期 17
·3588-3603
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IF 7.971
Liu Xiaochen,Cui Jianfeng,Gong Li,Tian Fei,Shen Yangli,Chen Lipeng,Wang Yong,Xia Yangyang,Liu Lei,Ye Xiang,Wang Molin,Liu Guangyi,Jiang Baichun,Shao Changshun,Zou Yongxin,Gong Yaoqin
CUL4B, which acts as a scaffold protein in CUL4B-RING ubiquitin ligase (CRL4B) complexes, participates in a variety of biological processes. Previous studies have shown that CUL4B is often overexpressed and exhibits oncogenic activities in a variety of solid tumors. However, the roles and the underlying mechanisms of CUL4B in bladder cancer (BC) were poorly understood. Here, we showed that CUL4B levels were overexpressed and positively correlated with the malignancy of BC, and CUL4B could confer BC cells increased motility, invasiveness, stemness, and chemoresistance. The PIK3CA/AKT pathway was identified as a critical downstream mediator of CUL4B-driven oncogenicity in BC cells. Furthermore, we demonstrated that CRL4B epigenetically repressed the transcription of miR-372/373, via catalyzing monoubiquitination of H2AK119 at the gene cluster encoding miR-372/373, leading to upregulation of PIK3CA and activation of AKT. Our findings thus establish a critical role for the CUL4B-miR-372/373-PIK3CA/AKT axis in the pathogenesis of BC and have important prognostic and therapeutic implications in BC.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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癌症研究
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产品关联
DOI
PubMed
高影响因子
RAPID COMMUNICATIONS IN MASS SPECTROMETRY
·
2017
·Vol. 32
·期 4
·342-348
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IF 1.998
Mengmeng Chen,Guohua Zhu,Jiaxiang Xu,Huarong Zhang,Jinsong Liu,Kezhi Jiang
Rationale Carcinogenic o -methylaniline is one of the banned aromatic amines in azo dyes, but it is very difficult to distinguish it from its noncarcinogenic isomers due to their identical retention time on chromatography and similar mass spectra. Methods Imidization of the isomeric methylanilines was carried out by treatment with benzaldehyde under mild conditions. The formed derivatives were analyzed by gas chromatography/mass spectrometry (GC/MS). Theoretical calculations were carried out on the Gaussian 03 program by using the density functional theory method at the B3LYP/6-311+G(d,p) level. Results Imidization of methylanilines occurred easily and gave rise to the corresponding N -methylbenzylidene benzenamines. The isomeric derivatives were completely separated by GC, and thus the three isomeric methylanilines could be determined simultaneously. Due to the ortho effect, the derivative from o -methylaniline has a characteristic fragment ion at m/z 118 with a stable bicyclic structure, and it could be easily differentiated from the meta - and para -isomers in electron ionization mass spectrometry. Conclusions These results provided a promising solution for simultaneous determination of isomeric methylanilines.
研究领域:
化学
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毒理学
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分析化学
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DOI
高影响因子
JOURNAL OF NANOPARTICLE RESEARCH
·
2020
·Vol. 22
·期 6
·1-16
·
IF 2.132
Liu Ying,Liu Susu,Wu Meiyu,Lv Jianjun,Yang Yanwei,Dan Mo,Liu Lin,Chen Liang,Wu Xiaochun,Fan Changfa,Xu Liming,Xie Liming
Benefited from their broad-spectrum antimicrobial property, silver nanoparticles (AgNPs) have been widely used in various daily life and medical products. Consequently, the bio-safety of AgNPs, especially long-term in vivo biological effects is of more and more importance. However, there are no correlated publications about AgNP carcinogenicity at present. Thus, in this study, we have investigated the potential carcinogenicity of polyvinylpyrrolidone (PVP)-coated AgNPs with an intermediate size (diameter ~ 42.5 nm). The C57- ras transgenic mouse model (CB6F1 Tg mice) harboring human c-Ha-ras gene was used to shorten the duration of in vivo experiments from 2 years to 22 weeks. CB6F1 Tg mice were intravenously injected by different single doses of AgNPs (0.4, 4, and 20 mg/kg body weight) during the 22-week carcinogenicity study. There were no obvious AgNP-related neoplastic lesions by microscope examination and no increase in the incidence of non-neoplastic lesions in the AgNP-treated mice in our study. Overall, these results indicate that AgNPs (≤ 20 mg/kg) do not cause carcinogenesis in CB6F1 Tg mice via a single-dose intravenous injection. This provides useful toxicological information and is of great importance to more applications of AgNPs in the future.
研究领域:
毒理学
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致癌作用
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纳米技术
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药理学
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产品关联
DOI
高影响因子
Virulence
·
2024
·
IF 5.5
Xiaofei Ji,Qianwen Wu,Xinying Cao,Shuzhen Liu,Jianhui Zhang,Si Chen,Jiangfan Shan,Ying Zhang,Boqing Li,Huilin Zhao
CagA is a significant oncogenic factor injected into host cells by Helicobacter pylori, which is divided into two subtypes: East Asian type (CagAE), characterized by the EPIYA-D motif, and western type (CagAW), harboring the EPIYA-C motif. CagAE has been reported to have higher carcinogenicity than CagAW, although the underlying reason is not fully understood. SHIP2 is an intracellular phosphatase that can be recruited by CagA to perturb the homeostasis of intracellular signaling pathways. In this study, we found that SHIP2 contributes to the higher oncogenicity of CagAE. Co-Immunoprecipitation and Pull-down assays showed that CagAE bind more SHIP2 than CagAW. Immunofluorescence staining showed that a higher amount of SHIP2 recruited by CagAE to the plasma membrane catalyzes the conversion of PI(3,4,5)P3 into PI(3,4)P2. This alteration causes higher activation of Akt signaling, which results in enhanced IL-8 secretion, migration, and invasion of the infected cells. SPR analysis showed that this stronger interaction between CagAE and SHIP2 stems from the higher affinity between the EPIYA-D motif of CagAE and the SH2 domain of SHIP2. Structural analysis revealed the crucial role of the Phe residue at the Y + 5 position in EPIYA-D. After mutating Phe of CagAE into Asp (the corresponding residue in the EPIYA-C motif) or Ala, the activation of downstream Akt signaling was reduced and the malignant transformation of infected cells was alleviated. These findings revealed that CagAE hijacks SHIP2 through its EPIYA-D motif to enhance its carcinogenicity, which provides a better understanding of the higher oncogenic risk of H. pylori CagAE.
研究领域:
微生物学
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分子生物学
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肿瘤学
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细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）