Cytotoxicity of an 125I-Labelled DNA Ligand

The subcellular distribution and cytotoxicity of a DNA-binding ligand [125I]-Hoechst 33258 following incubation of K562 cells with the drug was investigated. The ability of a radical scavenger, dimethyl sulphoxide, to protect cells from the 125I-decay induced cell death was also studied. Three diffe...

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Bibliographic Details
Published in:Acta oncologica 2000, Vol.39 (6), p.681-685
Main Authors: KARAGIANNIS, Tom C, LOBACHEVSKY, Pavel N, MARTIN, Roger F
Format: Article
Language:English
Subjects:
Apoptosis
Binding Sites
Biological and medical sciences
Bisbenzimidazole - toxicity
DNA Damage - genetics
DNA, Neoplasm - drug effects
DNA, Neoplasm - genetics
Fluorescent Dyes - toxicity
Humans
Iodine Radioisotopes - toxicity
K562 Cells - drug effects
Ligands
Medical sciences
Radiopharmaceuticals - toxicity
Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects)
Technology. Biomaterials. Equipments. Material. Instrumentation
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Summary:The subcellular distribution and cytotoxicity of a DNA-binding ligand [125I]-Hoechst 33258 following incubation of K562 cells with the drug was investigated. The ability of a radical scavenger, dimethyl sulphoxide, to protect cells from the 125I-decay induced cell death was also studied. Three different concentrations and specific activities of the drug were used to provide different ligand : DNA binding ratios. The results demonstrated a trend toward improved delivery of the ligand to the nucleus and to chromatin at higher ligand concentrations, with concomitant increased sensitivity to 125I-decay induced cytotoxicity and decreased protection by dimethyl sulphoxide. This correlation of radiobiological parameters with subcellular drug distribution is consistent with the classical dogma that attributes cytotoxicity to DNA double-stranded breakage in the vicinity of the site of decay, where the high LET nature of the damage confers minimal sensitivity to radical scavenging.
ISSN:0284-186X
1651-226X
DOI:10.1080/028418600750063721