Cytotoxicity of an 125I-labeled DNA-binding compound that induces double-stranded DNA breaks

[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.