Back to Search
Start Over
Role of DNA methylation in cell cycle arrest induced by Cr (VI) in two cell lines.
- Source :
-
PloS one [PLoS One] 2013 Aug 06; Vol. 8 (8), pp. e71031. Date of Electronic Publication: 2013 Aug 06 (Print Publication: 2013). - Publication Year :
- 2013
-
Abstract
- Hexavalent chromium [Cr(IV)], a well-known industrial waste product and an environmental pollutant, is recognized as a human carcinogen. But its mechanisms of carcinogenicity remain unclear, and recent studies suggest that DNA methylation may play an important role in the carcinogenesis of Cr(IV). The aim of our study was to investigate the effects of Cr(IV) on cell cycle progress, global DNA methylation, and DNA methylation of p16 gene. A human B lymphoblastoid cell line and a human lung cell line A549 were exposed to 5-15 µM potassium dichromate or 1.25-5 µg/cm² lead chromate for 2-24 hours. Cell cycle was arrested at G₁ phase by both compounds in 24 hours exposure group, but global hypomethylation occurred earlier than cell cycle arrest, and the hypomethylation status maintained for more than 20 hours. The mRNA expression of p16 was significantly up-regulated by Cr(IV), especially by potassium dichromate, and the mRNA expression of cyclin-dependent kinases (CDK4 and CDK6) was significantly down-regulated. But protein expression analysis showed very little change of p16 gene. Both qualitative and quantitative results showed that DNA methylation status of p16 remained unchanged. Collectively, our data suggested that global hypomethylation was possibly responsible for Cr(IV)-induced G₁ phase arrest, but DNA methylation might not be related to up-regulation of p16 gene by Cr(IV).
- Subjects :
- Cell Cycle drug effects
Cell Cycle genetics
Cell Line
Cyclin-Dependent Kinase 4 genetics
Cyclin-Dependent Kinase 4 metabolism
Cyclin-Dependent Kinase 6 genetics
Cyclin-Dependent Kinase 6 metabolism
Gene Expression Regulation drug effects
Genes, p16 drug effects
Humans
Promoter Regions, Genetic drug effects
Solubility
Carcinogens, Environmental toxicity
Cell Cycle Checkpoints drug effects
Cell Cycle Checkpoints genetics
Chromium toxicity
DNA Methylation physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 8
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 23940686
- Full Text :
- https://doi.org/10.1371/journal.pone.0071031