METHYL MERCURY AND DNA AND RNA SYNTHESIS IN VITRO

Project Details

Description

Methyl mercury (MeHg) has been shown to pose a severe health hazard and
environmental contamination with mercury represents an important public
health problem. Although there have been a number of studies on the
effects of MeHg on the cell, relatively little was preciously known about
its effects on cellular nucleic acid synthesis at the molecular level.
Previous workers have shown that methyl mercury inhibits the synthesis of
DNA and RNA in cells in culture. We have shown that in isolated nuclei it
also inhibits DNA synthesis, and some types of RNA synthesis, but
specifically stimulates synthesis catalyzed by RNA polymerase II. We have
obtained some information on the mechanism of this stimulation and intend
to pursue this further. Specifically we will investigate whether the
stimulation results from the MeHg-induced removal of histones from
chromatin. In addition, we will attempt to determine whether there are any
specific regions of the genome whose transcription is stimulated by MeHg.
We have shown that DNA treated with MeHg has higher template activity in an
RNA polymerase reaction, compared to untreated control DNA. An important
objective will be to investigate the mechanism of this effect. This will
involve studies on the kinetics and specificity of the formation of DNA
with increased template activity as well as its physical characterization.
Using the MeHg-treated DNA as a substrate we will attempt to detect an
enzymatic activity which can "repair" the MeHg-induced lesion, by assaying
for specific loss of template activity of the MeHg-treated DNA. Other
areas to be investigated are the interactions of MeHg with two selenium
compounds, selenite and selenate, in various in vitro systems of nucleic
acid synthesis which we have been utilizing. Also an apparent antagonistic
effect of MeHg on mammalian cell transformation and mutagenesis by MNNG
will be further investigated.
StatusFinished
Effective start/end date9/1/838/31/88

Funding

  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Environmental Science(all)
  • Medicine(all)

Fingerprint Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.