Abstract

The effect of the environmental pollutant and toxicant methylmercury on chromosome structure and function will be studied in cells of the continuous human cell line HeLa S3 (1) by analyzing, subsequent to methylmercury treatment, the fine structure as well as transcriptional activity of the cells' dispersed form of interphase nuclei (chromatin) with the aid of 'mapping' techniques (two-dimensional gel electrophoresis); (2) by monitoring the activity of the heavy metal-inducible metallothionein genes based on their capability to produce metallothionein mRNAs as well as metallothionein; and (3) by studying, in an extracellular system, the physico-chemical properties of nucleosomes, reassembled from the constituent chromosomal histone and non-histone proteins and DNA in the presence and absence of methylmercury, with the aid of thermal denaturation and circular dichroism measurements. It is the ultimate aim of this plan to provide, at the molecular level, a rationale for the finding that organomercurials in general, and methylmercury in particular, are powerful in vivo clastogens and teratogens (in addition to their also being powerful neurotoxicants).

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES003636-02
Application #
3251142
Study Section
Metallobiochemistry Study Section (BMT)
Project Start
1986-05-01
Project End
1989-04-30
Budget Start
1987-05-01
Budget End
1988-04-30
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
University of California Davis
Department
Type
Earth Sciences/Resources
DUNS #
094878337
City
Davis
State
CA
Country
United States
Zip Code
95618

  Publications

Gruenwedel, D W (1994) The mercury(II) and high-salt-induced conformational B<==>Z transitions of poly[d(G-m5C).d(G-m5C)] as studied by non-polarized (ultraviolet) and circularly polarized (CD) ultraviolet spectroscopy. Eur J Biochem 219:491-6
Gruenwedel, D W (1994) Effect of Hg(II) on the spectroscopic properties of poly[d(A-T).d(A-T] and poly[d(A).d(T)] and their constituent subunits (deoxyadenosine and thymidine monomers and dimers). Biophys Chem 52:115-23
Gruenwedel, D W (1994) Effect of Hg(II) on the spectroscopic properties of DNA bases: circular dichroism of deoxyadenosine and thymidine monomers and dimers. J Inorg Biochem 56:201-12
Ok, S R; Gruenwedel, D W (1993) Differential effect of Hg(II) on [d(A)n.d(T)n] and [d(A-T)n.d(A-T)n] sequences: circular dichroism (CD) measurements and endonuclease digestion studies using poly[d(A).d(T)] and poly[d(A-T).d(A-T)] as substrates. Z Naturforsch C 48:488-94
Gruenwedel, D W; Cruikshank, M K (1991) Changes in poly[d(T-G).d(C-A)] chirality due to Hg(II)-binding: circular dichroism (CD) studies. J Inorg Biochem 43:29-36
Gruenwedel, D W; Cruikshank, M K (1990) Mercury-induced DNA polymorphism: probing the conformation of Hg(II)-DNA via staphylococcal nuclease digestion and circular dichroism measurements. Biochemistry 29:2110-6
Gruenwedel, D W (1989) Hg(II)-induced changes in DNA-circular dichroism: reversible transitions between right-handed and left-handed screwness. Z Naturforsch C 44:1015-9
Gruenwedel, D W; Cruikshank, M K (1989) Mercury-induced transitions between right-handed and putative left-handed forms of poly[d(A-T).d(A-T)] and poly[d(G-C).d(G-C)] Nucleic Acids Res 17:9075-86