Effects of nickel on DNA methyltransferase activity and genomic DNA methylation levels

Yong Woo Lee, Limor Broday, Max Costa

Research output: Contribution to journalArticlepeer-review

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. Copyright (C) 1998 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)213-218
Number of pages6
JournalMutation Research - Genetic Toxicology and Environmental Mutagenesis
Volume415
Issue number3
DOIs
StatePublished - 31 Jul 1998
Externally publishedYes

Keywords

  • Carcinogenesis
  • Epigenetic
  • Nickel

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