کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5859205 | 1562333 | 2014 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Interindividual variation in response to xenobiotic exposure established in precision-cut human liver slices
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
LMPNAD(P)H dehydrogenase, quinone 1BNAglutathione S-transferase mu 1CDKN1ABPDEPHHcopy DNANQO1N-acetyl-p-benzoquinone imineNAPQIAPAPBMDBAPRT-PCRAFBCyPAHRNaOHHEPES2-nitrofluorene - 2-نیتروفلوئورن4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid - 4- (2-hydroxyethyl) -1-piperazineethanesulfonic acidcDNA - cDNADMSO - DMSOprimary human hepatocytes - hepatocytes اولیه انسانSmall interfering RNA - RNA تداخل کوچکsiRNA - siRNAAflatoxin B1 - آفلاتوکسین B1EDTA - اتیلن دی آمین تترا استیک اسید Ethylenediaminetetraacetic acid - اتیلینیدامین تتراستیک اسیدAcetaminophen - استامینوفن Critical Effect Size - اندازه اثر بحرانیCES - اینPrecision-cut liver slices - برش کبد دقیقGene expression - بیان ژنBayesian network analysis - تجزیه و تحلیل شبکه بیزیinterindividual variation - تنوع بین فردیbenchmark dose - دوز معادلDimethyl sulfoxide - دیمتیل سولفواکسیدSodium hydroxide, Caustic Soda - سدیم هیدروکسید، کاستیک سودا، سود سوزآورCarcinogens - سرطان زاCytochrome P450 - سیتوکروم پی۴۵۰Bayesian network - شبکه بیزی، شبکه بیزینEnzyme activity - فعالیت آنزیمlactate dehydrogenase - لاکتات دهیدروژناز LDH - لاکتات دهیدروژناز به صورت مختصر شده LDH cyclin-dependent kinase inhibitor 1A - مهار کننده 1A کیناز وابسته به کینازlow melting point - نقطه ذوب پایینreverse transcription polymerase chain reaction - واکنش زنجیره ای پلیمراز رونویسی معکوسaryl hydrocarbon receptor - گیرنده آرویل هیدروکربن
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Interindividual variation in response to xenobiotic exposure established in precision-cut human liver slices Interindividual variation in response to xenobiotic exposure established in precision-cut human liver slices](/preview/png/5859205.png)
چکیده انگلیسی
Large differences in toxicity responses occur within the human population. In this study we evaluate whether interindividual variation in baseline enzyme activity (EA)/gene expression (GE) levels in liver predispose for the variation in toxicity responses by assessing dose-response relationships for several prototypical hepatotoxicants. Baseline levels of cytochrome-P450 (CYP) GE/EA were measured in precision-cut human liver slices. Slices (n = 4-5/compound) were exposed to a dose-range of acetaminophen, aflatoxin B1, benzo(α) pyrene or 2-nitrofluorene. Interindividual variation in induced genotoxicity (COMET-assay and CDKN1A/p21 GE) and cytotoxicity (lactate dehydrogenase-leakage), combined with NQO1- and GSTM1-induced GE-responses for oxidative stress and GE-responses of several CYPs was evaluated. The benchmark dose-approach was applied as a tool to model exposure responses on an individual level. Variation in baseline CYP levels, both GE and EA, can explain variation in compound exposure-responses on an individual level. Network analyses enable the definition of key parameters influencing interindividual variation after compound exposure. For 2-nitrofluorene, this analysis suggests involvement of CYP1B1 in the metabolism of this compound, which represents a novel finding. In this study, GSTM1 which is known to be highly polymorphic within the human population, but so far could not be linked to toxicity in acetaminophen-poisoned patients, is suggested to cause interindividual variability in acetaminophen-metabolism, dependent on the individual's gene expression-responses of CYP-enzymes. This study demonstrates that using interindividual variation within network modelling provides a source for the definition of essential and even new parameters involved in compound-related metabolism. This information might enable ways to make more quantitative estimates of human risks.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology - Volume 323, 2 September 2014, Pages 61-69
Journal: Toxicology - Volume 323, 2 September 2014, Pages 61-69
نویسندگان
Marlon J.A. Jetten, Sandra M. Claessen, Cornelis H.C. Dejong, Agustin Lahoz, José V. Castell, Joost H.M. van Delft, Jos C.S. Kleinjans,