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HERO ID
1317796
Reference Type
Journal Article
Title
Effects of nickel on DNA methyltransferase activity and genomic DNA methylation levels
Author(s)
Lee, YW; Broday, L; Costa, M
Year
1998
Is Peer Reviewed?
1
Journal
Mutation Research
ISSN:
0027-5107
EISSN:
1873-135X
Report Number
EMIC/107376
Volume
415
Issue
3
Page Numbers
213-218
Language
English
PMID
9714811
Web of Science Id
WOS:000075259600005
Abstract
Methylation of DNA plays an important role in organizing the genome into transcriptionally active and inactive zones. Nickel compounds cause chromatin condensation and DNA methylation in the transgenic gpt+ Chinese hamster cell line (G12). Here we show that nickel is an inhibitor of cytosine 5-methyltransferase activity in vivo and in vitro. In living cells, this inhibition is transient and following a recovery period after nickel treatment, Mtase activity slightly rebounds. Genomic DNA methylation levels are also somewhat decreased following nickel treatment, but with time, there is an elevation of total DNA methylation above basal levels and before any rebound of methyltransferase activity. These results suggest that nickel exposure can elevate total genomic DNA methylation levels even when DNA methyltransferase activity is depressed. These findings may explain the hypermethylation of senescence and tumor suppressor genes found during nickel carcinogenesis and support the model of a direct effect of Ni2+ on chromatin leading to de novo DNA methylation.
Keywords
epigenetic; carcinogenesis; nickel
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