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 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.
Karagiannis
T C
TC
Trescowthick Research Laboratories, peter MacCallum Cancer Institute, Melbourne, Australia.
Lobachevsky
P N
PN
Martin
R F
RF
D017209:Apoptosis; D001665:Binding Sites; D006690:Bisbenzimidazole / Q000633:toxicity*; D004249:DNA Damage / Q000235:genetics*; D004273:DNA, Neoplasm / Q000187:drug effects / Q000235:genetics*; D005456:Fluorescent Dyes / Q000633:toxicity*; D006801:Humans; D007457:Iodine Radioisotopes / Q000633:toxicity*; D020014:K562 Cells / Q000187:drug effects; D008024:Ligands; D019275:Radiopharmaceuticals / Q000633:toxicity*
D004273:DNA, Neoplasm; D005456:Fluorescent Dyes; D007457:Iodine Radioisotopes; D008024:Ligands; D019275:Radiopharmaceuticals; D006690:Bisbenzimidazole