کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8456179 | 1548539 | 2018 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Reprint of: A three-dimensional in vitro HepG2 cells liver spheroid model for genotoxicity studies
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کلمات کلیدی
ECMCBMNCBPICYP450 enzymesOECDPhIPRT-PCRBCGCyPAHRThree-dimensionalB[a]P - B [a] PDMSO - DMSOEDTA - اتیلن دی آمین تترا استیک اسید Ethylenediaminetetraacetic acid - اتیلینیدامین تتراستیک اسیدBromocresol green - بروموکرزول سبزBenzo[a]pyrene - بنزو [a] پییرنstandard error - خطای استانداردtwo-dimensional - دو بعدیDimethyl sulfoxide - دیمتیل سولفواکسیدOrganization for Economic Co-operation and Development - سازمان همکاری و توسعه اقتصادیGenotoxicity - سمیت ژنتیکیCytochrome P450 - سیتوکروم پی۴۵۰Cytokinesis-block proliferation index - شاخص تکثیر بلوک سیتوکینزیسMetabolic activation - فعال سازی متابولیکExtracellular matrix - ماتریکس خارج سلولیMicronucleus - میکروسکوپreverse transcription polymerase chain reaction - واکنش زنجیره ای پلیمراز رونویسی معکوسPropidium iodide - پروتئین یدیدGenotoxicants - ژنتیکaryl hydrocarbon receptor - گیرنده آرویل هیدروکربن
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Reprint of: A three-dimensional in vitro HepG2 cells liver spheroid model for genotoxicity studies Reprint of: A three-dimensional in vitro HepG2 cells liver spheroid model for genotoxicity studies](/preview/png/8456179.png)
چکیده انگلیسی
The liver's role in metabolism of chemicals makes it an appropriate tissue for toxicity testing. Current testing protocols, such as animal testing and two-dimensional liver cell systems, offer limited resemblance to in vivo liver cell behaviour, in terms of gene expression profiles and metabolic competence; thus, they do not always accurately predict human toxicology. In vitro three-dimensional liver cell models offer an attractive alternative. This study reports on the development of a 3D liver model, using HepG2 cells, by a hanging-drop technique, with a focus on evaluating spheroid growth characteristics and suitability for genotoxicity testing. The cytokinesis-blocked micronucleus assay protocol was adapted to enable micronucleus (MN) detection in the 3D spheroid models. This involved evaluating the difference between hanging vs non-hanging drop positions for dosing of the test agents and comparison of automated Metafer scoring with manual scoring for MN detection in HepG2 spheroids. The initial seeding density, used for all experiments, was 5000 cells/20â¯Î¼l drop hanging spheroids, harvested on day 4, with >75% cell viability. Albumin secretion (7.8â¯g/l) and both CYP1A1 and CYP1A2 gene expression were highest in the 3D environment at day 4. Exposure to metabolically activated genotoxicants for 24â¯h resulted in a 6-fold increase in CYP1A1 enzyme activity (3â¯Î¼M B[a]P) and a 30-fold increase in CYP1A2 enzyme activity (5â¯Î¼M PhIP) in 3D hanging spheroids. MN inductions in response to B[a]P or PhIP were 2-fold and 3-fold, respectively, and were greater in 3D hanging spheroids than in 2D format, showing that hanging spheroids are more sensitive to genotoxic agents. HepG2 hanging-drop spheroids are an exciting new alternative system for genotoxicity studies, due to their improved structural and physiological properties, relative to 2D cultures.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Mutation Research/Genetic Toxicology and Environmental Mutagenesis - Volume 834, October 2018, Pages 35-41
Journal: Mutation Research/Genetic Toxicology and Environmental Mutagenesis - Volume 834, October 2018, Pages 35-41
نویسندگان
Ume-Kulsoom Shah, Jefferson de Oliveira Mallia, Neenu Singh, Katherine E. Chapman, Shareen H. Doak, Gareth J.S. Jenkins,