کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5859287 1562341 2014 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Fumonisin B1 induces global DNA hypomethylation in HepG2 cells - An alternative mechanism of action
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Fumonisin B1 induces global DNA hypomethylation in HepG2 cells - An alternative mechanism of action
چکیده انگلیسی

Fumonisin B1 (FB1), a common mycotoxin contaminant of maize, is known to inhibit sphingolipid biosynthesis and has been implicated in cancer promoting activity in animals and humans. FB1 disrupts DNA methylation and chromatin modifications in human hepatoma (HepG2) cells. We investigated the effect of FB1 on enzymes, DNA methyltransferases and demethylases, involved in chromatin maintenance and gross changes in structural integrity of DNA in HepG2 cells. We measured: (i) the expression of 84 key genes encoding enzymes known to modify genomic DNA and histones (superarray and qPCR); (ii) protein expression of DNA methyltransferases (DNMT1, DNMT3A and DNMT3B) and the major demethylase (MBD2) (western blotting); (iii) degree of DNA methylation by FACS using anti-5-MeCyt and (iv) DNA migration (single cell gel electrophoresis). FB1 significantly decreased the methyltransferase activities of DNMT1, DNMT3A and DNMT3B, and significantly up regulated the demethylases (MBD2 expression and activity, and KDM5B and KDM5C expression). FACS data showed FB1 significantly increased DNA hypomethylation and resulted in gross changes in structural DNA as evidenced by the Comet assay. We conclude that FB1 induces global DNA hypomethylation and histone demethylation that causes chromatin instability and may lead to liver tumourigenesis.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology - Volume 315, 6 January 2014, Pages 65-69
نویسندگان
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