title: Cytotoxicity of an 125I-labeled DNA-binding compound that induces double-stranded DNA breaks.
abstract: [125I]Iodorivanol (6,9-diamino-2-ethoxy-5-[125]iodoacridine) has been prepared by direct iodination of rivanol (6.9-diamino-2-ethoxyacridine). In vitro binding of [125I]iodorivanol to PM2 DNA resulted in induction of double-stranded DNA breaks following decay of the 125I atom, presumably in the same way as decay of 125I atoms in 125I-labeled DNA causes double-stranded DNA breaks. Treatment of mouse L-cell cultures with [125I]iodorivanol resulted in a cell kill, the extent of which was dependent on the 125I specific activity and the duration of exposure. A clonogenic assay was used to quantitate cell kill. It was concluded that at least some of the [125I]iodorivanol in the culture medium was taken up by the cells, transported to the nucleus, and bound to DNA and that subsequent decay of the 125I atoms induced double-stranded DNA breaks in the genome, with consequent loss of viability. 125I-labeled DNA-binding compounds are suggested as a novel class of cytotoxic agents.
mesh_terms: D000166:Acridines / Q000494:pharmacology*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects* / Q000528:radiation effects; D004247:DNA / Q000378:metabolism*; D004975:Ethacridine / Q000031:analogs & derivatives / Q000494:pharmacology*; D007457:Iodine Radioisotopes / Q000008:administration & dosage*; D007739:L Cells / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D051379:Mice
chemical_list: D000166:Acridines; D007457:Iodine Radioisotopes; C020372:iodorivanol; D004247:DNA; D004975:Ethacridine