林丹与抗生素对黑腹果蝇肿瘤细胞迁移的联合毒性与氧化应激效应研究
Combined Effects of Lindane and Antibiotics on Tumor Migration and Antioxidant Responses in Drosophila melanogaster
-
摘要: 有机氯农药(OCPs)与抗生素分别代表持久性有机污染物与新污染物，二者共存于环境介质中，然而其联合毒性尚缺乏系统研究。围绕癌症发生与治疗中的关键环节肿瘤细胞迁移效应，以林丹代表OCPs，以磺胺甲恶唑(SMX)、盐酸四环素(TET)代表抗生素，基于黑腹果蝇模式生物，探究林丹及其与SMX或TET的二元混合物的联合效应。单独暴露的效应表明，林丹在40～100 ng·g-1浓度范围内显著增强了果蝇幼虫眼部与脑部肿瘤细胞向前庭核复合体(VNC)的迁移率(P<0.05)，该效应随浓度升高逐渐增强；SMX在最高浓度组400 ng·g-1显著增强了肿瘤细胞迁移水平；TET在600～1 000 ng·g-1显著增强了肿瘤细胞迁移，并表现出浓度依赖关系。采用直接均分法设计的二元混合物效应表明，林丹与SMX或TET的二元混合物都显著增强了肿瘤细胞迁移水平，随着林丹浓度的升高，肿瘤细胞迁移效应也逐渐增强；与独立作用(IA)模型预测值相比，混合物均表现出协同作用。对氧化应激相关指标的检测表明，林丹、SMX、TET以及二元混合物普遍增加了活性氧自由基(ROS)，减少了谷胱甘肽(GSH)。林丹与SMX的联合作用中肿瘤细胞迁移效应与过氧化氢酶(CAT)呈负相关，林丹与TET的联合作用并未表现如此相关性，该差异与SMX、TET诱发氧化应激效应存在差异有关。同时，林丹与SMX、林丹与TET这2类二元混合物的效应表现出不同的层次聚类分析结果。林丹与SMX联合作用诱发的肿瘤细胞迁移效应与ROS和超氧化物歧化酶(SOD)有相似聚类关系，林丹与TET联合作用诱发的肿瘤细胞迁移效应与ROS表现出最相近的聚类关系。该结果再次表明SMX、TET氧化应激效应的不同对其与林丹联合作用的影响，也表明抗生素类别可显著影响混合物潜在致毒途径。Abstract: Organic chlorine pesticides (OCPs) and antibiotics represent persistent organic pollutants and emerging pollutants, respectively. They can coexist in various environmental matrix, while their combined effects were seldom explored. Lindane was chosen to represent OCPs, and sulfamethoxazole (SMX) and tetracycline hydrochloride (TET) were chosen to represent antibiotics. The present study focused on the influences on tumor migration which is essential for both carcinogenesis and cancer treatment and aimed to explore the effects of the binary mixtures on the model organism Drosophila melanogaster. The individual effects showed that lindane significantly enhanced the tumor migration from the eye and brain of the larvae to the ventral nerve cord (VNC) in the concentration range of 40～100 ng·g-1 (P<0.05). SMX enhanced the tumor migration at the highest concentration of 400 ng·g-1, while TET increased the tumor migration from 600 to 1 000 ng·g-1 with a concentration-dependence. The binary mixtures were designed by direct equipartition method. The binary mixtures that contained lindane and SMX or TET significantly enhanced the tumor migration, with a dependence on the lindane’s concentrations. Compared with the predicted effects by independent action (IA) model, the binary mixtures showed synergistic toxicity interactions. Determination on the antioxidant responses showed that, lindane, SMX, TET and the binary mixtures commonly increased reactive oxygen species (ROS) while decreased glutathione (GSH). The effects of binary mixtures containing lindane and SMX on tumor migration were negatively correlated with their influences on catalase (CAT) activities, while such correlation was not observed in the effects of mixtures containing lindane and TET. Such difference was attributed to the different effects of SMX and TET on the antioxidants. Moreover, the effects of binary mixtures containing lindane and SMX, and those containing lindane and TET showed different hierarchical clustering positions. The effects of binary mixtures containing lindane and SMX on tumor migration were closely connected with both ROS and superoxide dismutase (SOD), while those of binary mixtures containing lindane and TET were closely connected with ROS. Such differences supported the attribution to the individual effects of SMX or TET on the antioxidants and also indicated that the antibiotic types can influence the toxicity mechanism of the binary mixtures.
-
-
Abass K, Unguryanu T, Junqué E, et al. Pilot study on the concentrations of organochlorine compounds and potentially toxic elements in pregnant women and local food items from the Finnish Lapland [J]. Environmental Research, 2022, 211: 113122 刘明丽. 长江流域水相、沉积相中多溴联苯醚及有机氯农药的污染特征和风险评价[D]. 北京: 北京交通大学, 2018 Liu M L. Characteristics and risk assessment of polybrominated diphenyl ethers and organochlorine pesticides in water and sediment of the Yangtze River Basin [D]. Beijing: Beijing Jiaotong University, 2018 (in Chinese) 周晓芳, 高良敏, 陈晓晴, 等. 杨庄煤矿区农田塌陷水域多介质OCPs污染特征及生态风险研究[J]. 农业环境科学学报, 2020, 39(5): 1085-1093 Zhou X F, Gao L M, Chen X Q, et al. Pollution characteristics and ecological risks of organochlorine pesticides in multiple-media of farmland subsidence water in Yangzhuang coal mine area, China [J]. Journal of Agro-Environment Science, 2020, 39(5): 1085-1093 (in Chinese)
魏抱楷. 典型有毒有机污染物在农作物中迁移规律的研究[D]. 北京: 中央民族大学, 2020 Wei B K. Study on the migration law of typical toxic organic pollutants in crops [D]. Beijing: Central University for Nationalities, 2020 (in Chinese) Vijgen J, Fokke B, van de Coterlet G, et al. European cooperation to tackle the legacies of hexachlorocyclohexane (HCH) and lindane [J]. Emerging Contaminants, 2022, 8: 97-112 Polanco Rodríguez Á G, Riba López M I, DelValls Casillas T Á, et al. Monitoring of organochlorine pesticides in blood of women with uterine cervix cancer [J]. Environmental Pollution, 2017, 220(Pt B): 853-862 Loomis D, Guyton K, Grosse Y, et al. Carcinogenicity of lindane, DDT, and 2,4-dichlorophenoxyacetic acid [J]. The Lancet Oncology, 2015, 16(8): 891-892 Eissa F, Ghanem K, Al-Sisi M. Occurrence and human health risks of pesticides and antibiotics in Nile tilapia along the Rosetta Nile Branch, Egypt [J]. Toxicology Reports, 2020, 7: 1640-1646 Tang J P, Wang S, Tai Y P, et al. Evaluation of factors influencing annual occurrence, bioaccumulation, and biomagnification of antibiotics in planktonic food webs of a large subtropical river in South China [J]. Water Research, 2020, 170: 115302 Jansomboon W, Boontanon S K, Boontanon N, et al. Monitoring and determination of sulfonamide antibiotics (sulfamethoxydiazine, sulfamethazine, sulfamethoxazole and sulfadiazine) in imported Pangasius catfish products in Thailand using liquid chromatography coupled with tandem mass spectrometry [J]. Food Chemistry, 2016, 212: 635-640 Liu Y H, Chen Y, Feng M J, et al. Occurrence of antibiotics and antibiotic resistance genes and their correlations in river-type drinking water source, China [J]. Environmental Science and Pollution Research International, 2021, 28(31): 42339-42352 Gu J Y, Chen C Y, Huang X Y, et al. Occurrence and risk assessment of tetracycline antibiotics in soils and vegetables from vegetable fields in Pearl River Delta, South China [J]. Science of the Total Environment, 2021, 776: 145959 Yang Y, Qiu W Q, Li Y X, et al. Antibiotic residues in poultry food in Fujian Province of China [J]. Food Additives & Contaminants Part B, Surveillance, 2020, 13(3): 177-184 Zainab S M, Junaid M, Xu N, et al. Antibiotics and antibiotic resistant genes (ARGs) in groundwater: A global review on dissemination, sources, interactions, environmental and human health risks [J]. Water Research, 2020, 187: 116455 冯琳钧, 许瀚文, 王艺霏, 等. 3种β-内酰胺类抗生素对大型溞毒性影响的研究[J]. 环境科学与技术, 2020, 43(12): 1-7 Feng L J, Xu H W, Wang Y F, et al. Effects of three β-lactam antibiotics on Daphnia magna toxicity [J]. Environmental Science & Technology, 2020, 43(12): 1-7 (in Chinese)
杜明磊. 三种抗生素对两种纤毛虫的毒性效应研究[D]. 哈尔滨: 哈尔滨师范大学, 2020 Du M L. Research on the toxicity of three antibiotics to two ciliates [D]. Harbin: Harbin Normal University, 2020 (in Chinese) 钱坤, 任连泉, 王敬, 等. 常见抗生素类兽药对作物的遗传毒性研究分析[J]. 畜禽业, 2020, 31(4): 23 Qian K, Ren L Q, Wang J, et al. Study on genetic toxicity of common antibiotic veterinary drugs to crops [J]. Livestock and Poultry Industry, 2020 , 31(4): 23 (in Chinese)
刘仁彬, 姜锦林, 张宇峰, 等. 磺胺甲恶唑对斑马鱼胚胎/仔鱼的毒性效应[J]. 环境污染与防治, 2020, 42(3): 310-316 Liu R B, Jiang J L, Zhang Y F, et al. Toxic effects of sulfamethoxazole on zebrafish (Danio rerio) embryo/larva [J]. Environmental Pollution & Control, 2020, 42(3): 310-316 (in Chinese)
Zhang L W, Zhu Z J, Yan H W, et al. Creatine promotes cancer metastasis through activation of Smad2/3 [J]. Cell Metabolism, 2021, 33(6): 1111-1123.e4 Gui P, Bivona T G. Evolution of metastasis: New tools and insights [J]. Trends in Cancer, 2022, 8(2): 98-109 沈佳颖, 于振洋, 尹大强, 等. 林丹通过MAPK和UPR通路与干扰线粒体功能诱导黑腹果蝇(Drosophila melanogaster)肿瘤细胞迁移[J]. 生态毒理学报, 2018, 13(5): 97-109 Shen J Y, Yu Z Y, Yin D Q, et al. Tumor cell migration of Drosophila melanogaster by lindane exposure with involvement of MAPK and UPR pathways and mitochondrial dysfunction [J]. Asian Journal of Ecotoxicology, 2018, 13(5): 97-109 (in Chinese)
Pinato D J, Howlett S, Ottaviani D, et al. Association of prior antibiotic treatment with survival and response to immune checkpoint inhibitor therapy in patients with cancer [J]. JAMA Oncology, 2019, 5(12): 1774-1778 Cai J H, Xia L M, Li J L, et al. Tumor-associated macrophages derived TGF-β-induced epithelial to mesenchymal transition in colorectal cancer cells through Smad2,3-4/snail signaling pathway [J]. Cancer Research and Treatment, 2019, 51(1): 252-266 Liao Z H, Chua D, Tan N S. Reactive oxygen species: A volatile driver of field cancerization and metastasis [J]. Molecular Cancer, 2019, 18(1): 65 Blazquez R, Rietkötter E, Wenske B, et al. LEF1 supports metastatic brain colonization by regulating glutathione metabolism and increasing ROS resistance in breast cancer [J]. International Journal of Cancer, 2020, 146(11): 3170-3183 Ogata F T, Simões Sato A Y, Coppo L, et al. Thiol-based antioxidants and the epithelial/mesenchymal transition in cancer [J]. Antioxidants & Redox Signaling, 2022, 36(13-15): 1037-1050 Zińczuk J, Maciejczyk M, Zaręba K, et al. Pro-oxidant enzymes, redox balance and oxidative damage to proteins, lipids and DNA in colorectal cancer tissue. Is oxidative stress dependent on tumour budding and inflammatory infiltration? [J]. Cancers, 2020, 12(6): 1636 Otsmane A, Kacimi G, Adane S, et al. Clinico-epidemiological profile and redox imbalance of lung cancer patients in Algeria [J]. Journal of Medicine and Life, 2018, 11(3): 210-217 Yu Y J, Chen H B, Hua X, et al. Long-term toxicity of lindane through oxidative stress and cell apoptosis in Caenorhabditis elegans [J]. Environmental Pollution, 2021, 272: 116036 Zheng Y G, Yu Z Y, Zhang J. Multi-generational effects of enrofloxacin on lifespan and reproduction of Caenorhabditis elegans with SKN-1-mediated antioxidant responses and lipid metabolism disturbances [J]. Science of the Total Environment, 2022, 804: 150250 Srivastava A. A protocol for genetic induction and visualization of benign and invasive tumors in cephalic complexes of Drosophila melanogaster [J]. Journal of Visualized Experiments, 2013, 79: 50624 Yu Z Y, Shen J Y, Li Z, et al. Obesogenic effect of sulfamethoxazole on Drosophila melanogaster with simultaneous disturbances on eclosion rhythm, glucolipid metabolism, and microbiota [J]. Environmental Science & Technology, 2020, 54(9): 5667-5675 Dou R N, Liu S S, Mo L Y, et al. A novel direct equipartition ray design (EquRay) procedure for toxicity interaction between ionic liquid and dichlorvos [J]. Environmental Science and Pollution Research International, 2011, 18(5): 734-742 刘树深, 刘玲, 陈浮. 浓度加和模型在化学混合物毒性评估中的应用[J]. 化学学报, 2013, 71(10): 1335-1340 Liu S S, Liu L, Chen F. Application of the concentration addition model in the assessment of chemical mixture toxicity [J]. Acta Chimica Sinica, 2013, 71(10): 1335-1340 (in Chinese)
Yu Z Y, Yin D Q, Hou M F, et al. Effects of food availability on the trade-off between growth and antioxidant responses in Caenorhabditis elegans exposed to sulfonamide antibiotics [J]. Chemosphere, 2018, 211: 278-285 Han T, Liang Y P, Wu Z N, et al. Effects of tetracycline on growth, oxidative stress response, and metabolite pattern of ryegrass [J]. Journal of Hazardous Materials, 2019, 380: 120885 Man Y C, Zhang H, Huang J, et al. Combined effect of tetracycline and copper ion on catalase activity of microorganisms during the biological phosphorus removal [J]. Journal of Environmental Management, 2022, 304: 114218 Garrido-Mesa J, Algieri F, Rodríguez-Nogales A, et al. Immunomodulatory tetracyclines ameliorate DNBS-colitis: Impact on microRNA expression and microbiota composition [J]. Biochemical Pharmacology, 2018, 155: 524-536 Boonma T, Navasumrit P, Parnlob V, et al. SAM and folic acid prevent arsenic-induced oxidative and nitrative DNA damage in human lymphoblast cells by modulating expression of inflammatory and DNA repair genes [J]. Chemico-Biological Interactions, 2022, 361: 109965 Nadeesha Dilrukshi H N, Torrico D D, Brennan M A, et al. Effects of extrusion processing on the bioactive constituents, in vitro digestibility, amino acid composition, and antioxidant potential of novel gluten-free extruded snacks fortified with cowpea and whey protein concentrate [J]. Food Chemistry, 2022, 389: 133107 Andlid T A, D’Aimmo M R, Jastrebova J. Folate and Bifidobacteria [M]. Pittsburg: Academic Press, 2018: 195-212 -
点击查看大图
计量
- 文章访问数: 1704
- HTML全文浏览数: 1704
- PDF下载数: 63
- 施引文献: 0
下载:
