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.
|Effective start/end date||1/1/90 → 1/1/90|
- National Institute of Environmental Health Sciences
- Cell Biology
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