کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2602439 1562715 2015 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Cadmium affects mitotically inherited histone modification pathways in mouse embryonic stem cells
ترجمه فارسی عنوان
کادمیوم مسیرهای اصلاح شده هیستون را در سلول های بنیادی جنینی موش های منتسب به میتوتاسیون تأثیر می گذارد
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
چکیده انگلیسی


• Cd toxicity is mitotically inherited in stem cell cultures and expressed in alternate passages as H3K27me1 modification.
• Cd preferentially affects S phase of the stem cell cycle.
• Cd preferentially suppresses chromatin stability.
• Epigenetic toxicity in stem cells depends on cellular differentiation.

The fetal basis of adult disease (FeBAD) theorizes that embryonic challenges initiate pathologies in adult life through epigenetic modification of gene expression. In addition, inheritance of H3K27 methylation marks, especially in vitro, is still controversial. Metals, such as Cd, are known to affect differentiation, DNA repair and epigenetic status in mES cells. We tested the premise that Cd exerts differential toxicity in mouse embryonic stem (mES) cells by targeting total histone protein (THP) production early in stem cell development, while affecting H3K27-mono-methylation (H3K27me1) in latter stages of differentiation. The inability of mES cells to recover from Cd insult at concentrations greater than IC50 indicates that maximum cytotoxicity occurs during initial hours of exposure. Moreover, as a measure of chromatin stability, low dose acute Cd exposure lowers THP production. The heritable effects of Cd exposure on cell proliferation, chromatin stability and transcription observed through several cell population doublings were detected only during alternate passages on days 3, 7, and 11, presumably due to slower maturation of histone methylation marks. These findings demonstrate a selective disruption of chromatin structure following acute Cd exposure, an effect not seen in developmentally mature cells. Hence, we present that acute Cd toxicity is cumulative and disrupts DNA repair, while concurrently affecting cell cycle progression, chromatin stability and transcriptional state in mES cells.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology in Vitro - Volume 30, Issue 1, Part B, 25 December 2015, Pages 583–592
نویسندگان
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