کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8551041 | 1562106 | 2018 | 15 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Minimum datasets to establish a CAR-mediated mode of action for rodent liver tumors
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کلمات کلیدی
EPAEGFECHAAOPPRODMOANitrapyrin5-bromo-2′-deoxyuridine - 5-bromo-2'-deoxyuridine5-ethynyl-2′-deoxyuridine - 5-ethynyl-2'-deoxyuridineEdU - EDUEnvironmental Protection Agency - آژانس حفاظت از محیط زیستEuropean Chemicals Agency - آژانس مواد شیمیایی اروپاBROD - برادBrdU - بروموداکسی اوریدینTumor - تومورRodent - جوندگانMode of action - حالت عملKey event - رویداد کلیدیepidermal growth factor - عامل رشد اپیدرمیPhenobarbital - فنوباربیتالCAR - ماشینadverse outcome pathway - مسیر ناخوشایندknockout - ناکاوتLiver - کبدconstitutive androstane receptor - گیرنده آندروستان پایدار
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Minimum datasets to establish a CAR-mediated mode of action for rodent liver tumors Minimum datasets to establish a CAR-mediated mode of action for rodent liver tumors](/preview/png/8551041.png)
چکیده انگلیسی
Methods for investigating the Mode of Action (MoA) for rodent liver tumors via constitutive androstane receptor (CAR) activation are outlined here, based on current scientific knowledge about CAR and feedback from regulatory agencies globally. The key events (i.e., CAR activation, altered gene expression, cell proliferation, altered foci and increased adenomas/carcinomas) can be demonstrated by measuring a combination of key events and associative events that are markers for the key events. For crop protection products, a primary dataset typically should include a short-term study in the species/strain that showed the tumor response at dose levels that bracket the tumorigenic and non-tumorigenic dose levels. The dataset may vary depending on the species and the test compound. As examples, Case Studies with nitrapyrin (in mice) and metofluthrin (in rats) are described. Based on qualitative differences between the species, the key events leading to tumors in mice or rats by this MoA are not operative in humans. In the future, newer approaches such as a CAR biomarker signature approach and/or in vitro CAR3 reporter assays for mouse, rat and human CAR may eventually be used to demonstrate a CAR MoA is operative, without the need for extensive additional studies in laboratory animals.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Regulatory Toxicology and Pharmacology - Volume 96, July 2018, Pages 106-120
Journal: Regulatory Toxicology and Pharmacology - Volume 96, July 2018, Pages 106-120
نویسندگان
Richard C. Peffer, Matthew J. LeBaron, Michael Battalora, Werner H. Bomann, Christoph Werner, Manoj Aggarwal, Rocky R. Rowe, Helen Tinwell,