zinostatin and talisomycin

Methods for determining sequence specificities of anticancer drugs, carcinogens, and mutagens which interact with natural DNA's are presented. For drugs which nick or covalently bind to DNA and thus leave a permanent record of their residence position on the helix, the sequences important in drug action can be readily determined. For agents which interact with DNA in an equilibrium fashion, "footprinting" analysis, a technique used to investigate protein-DNA binding, has proved to be useful in studying drug-DNA interactions. The sequence specificities of a number of small ligands which interact with natural DNA's are also presented.

Topics: Anti-Bacterial Agents; Base Sequence; Bleomycin; Cisplatin; Dactinomycin; Distamycins; DNA; DNA Restriction Enzymes; Doxorubicin; Edetic Acid; Humans; Iron; Methods; Micrococcal Nuclease; Netropsin; Organometallic Compounds; Peptides; Pharmaceutical Preparations; Phenanthrolines; Phleomycins; Plicamycin; Substrate Specificity; Zinostatin

Cytogenetic damage in cells cultured from normal individuals and patients with ataxia telangiectasia (A-T) and xeroderma pigmentosum (XP) was induced by the chemotherapeutic antibiotics neocarzinostatin (NCS), tallysomycin (TLM) and bleomycin (BLM). Chromosomal breakage was specifically elevated in A-T cells when compared to the other genotypes tested. Similar results were not observed with the clastogens mitomycin C (MMC) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) as all cells responded similarly. All 5 chemical agents caused a marked suppression of de novo DNA synthesis in normal and XP long-term lymphoid cell lines while the A-T cells seemed resistant to this effect of NCS, TLM and BLM.

Topics: Antibiotics, Antineoplastic; Ataxia Telangiectasia; Bleomycin; Cells, Cultured; Chromosome Aberrations; DNA; DNA Repair; Humans; Mutation; Zinostatin