Genetic Response to Metals

Part 1 Molecular mechanism of metal induced mutagenicity and carcinogenicity: regulation of nuclear calcium and zinc interference by toxic metal ions; effects of antioxidants, zinc, and chelators on free radical status of children living in the chernobyl area; the role of ascorbate in metabolism and geno-toxicity of chromium (VI); inactivation of critical cancer-related genes by nickel-induced DNA hypermethylation and increased chromatin condensation - a new model for epigenetic carcinogenesis; oxidative mechanisms of nickel(II) and cobalt(II) genotoxicity; the antimutagenic effects of metallothionein may involve free radical scavenging; protection from metal-induced DNA damage by metallothionein in an in vitro system; DNA strand breakage and lipid peroxidation as possible mechanisms of selenium toxicity; role of metal in oxidative DNA damage by nonmutagenic carcinogen. Part 2 Metal-DNA, DNA cleavage, and zinc-finger proteins: sequence-selective cleavage of DNA by cationic metalloporphyrins; lanthanide(III) complexes as synthetic nucleases - hydroxyalkyl group participation in catalysis; initiation of DNA strand cleavage by iron bleomycin - key role of DNA in determining the pathway of reaction; nickel complexes in modification of nucleic acids; new methods for determining the structure of DNA and DNA-protein complexes based on the chemistry of iron(II) EDTA; DNA recognition by steroid hormone receptor zinc fingers - effects of metal replacement and protein-protein dimerization interface; HIV-1 tat protein forms a zinc-finger-like structure. Part 3 Metal-related genetic diseases - Menkes and Wilson diseases: Menkes disease - from patients to gene; variability in clinical expression of an X-linked copper disturbance, Menkes disease; development of copper-histidine treatment for Menkes disease; copper-histidine therapy in Menkes disease - clinical, biochemical, and molecular aspects; biochemical and clinical benefits of copper-histidine therapy in Menkes disease; the Wilson disease gene - a copper-binding ATPase homologous to the Menkes disease gene; zinc therapy - an advance in the treatment of Wilson's disease. Part 4 Metals and gene regulation: transcriptional regulation and function of yeast metallothionein genes; transcriptional regulation of the metallothionein gene - metal-responsive element and zinc regulatory factor.