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HERO ID
2219793
Reference Type
Journal Article
Title
Changes of c-Myc and DNMT1 mRNA and protein levels in the rat livers induced by dibutyl phthalate treatment
Author(s)
Urbanek-Olejnik, K; Liszewska, M; Winczura, A; Kostka, G
Year
2016
Is Peer Reviewed?
Yes
Journal
Toxicology and Industrial Health
ISSN:
0748-2337
EISSN:
1477-0393
Volume
32
Issue
5
Page Numbers
801-808
Language
English
PMID
24311629
DOI
10.1177/0748233713512363
Web of Science Id
WOS:000375578200005
URL
https://search.proquest.com/docview/1787984208?accountid=171501
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Abstract
We investigated the relationship between dibutyl phthalate (DBP)-induced hypomethylation of the c-Myc promoter region (as evident in our early study) and the expression of c-Myc and DNMT1 genes (at messenger RNA (mRNA) and protein level) in the rat liver. Male Wistar rats received DBP in 1, 3, or 14 daily doses of 1800 mg kg(-1) body weight. Levels of DNMT1, c-Myc mRNA, and proteins were detected using real-time polymerase chain reaction and Western blot analysis, respectively. Our findings indicate that DBP caused an increase in mRNA levels of c-Myc at all time points. The results showed that protein levels of c-Myc in rat liver also increased significantly by DBP treatment, which were more pronounced at last time point (after 14 doses). Furthermore, overexpression of DNMT1gene have been found after one dose of DBP, which was confirmed at the protein level by Western blot analysis. Reduced levels of DNMT1mRNA and proteins (3 and 14 doses) were coordinated with depletion DNA synthesis (reported previously). Based on our previous results and those presented here, the following conclusion could be drawn: (1) DBP exerted biological activity through epigenetic modulation of c-Myc gene expression; (2) it seems possible that DBP-induced active demethylation of c-Myc gene through mechanism(s) linked to generation of reactive oxygen species by activated c-Myc; and (3) control of DNA replication was not directly dependent on c-Myc transcriptional activity and we attribute this finding to DNMT1gene expression which was tightly coordinated with DNA synthesis.
Keywords
Gene expression; c-Myc; DNMT1; DBP; rat; liver
Tags
IRIS
•
Dibutyl Phthalate (DBP)
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