Crosslinking of cellular DNA by nitracrine and furocoumarin derivatives

The anticancer drug, nitracrine, a 1-nitro-9-aminoalkyl derivative of acrid ine exhibits potent cytotoxic effects which are due to its metabolic activa tion, followed by covalent binding to macromolecules - DNA being the target for the drug. The renaturable fraction of DNA from L-1210 cells pretreated with nitracrine is assayed by means of ethidium bromide fluorescence assay and chromatography on hydroxyapatite column. The effect of the drug was co mpared with furocoumarins of different DNA crosslinking potencies. The exis tence of crosslinks in DNA upon incubation of cells with nitracrine (1-4 mu M) have been confirmed with two different methods under the conditions whe re 8-methoxypsoralen, a classic crosslinking agent induced the renaturation . The DNA preparation isolated from the drug pretreated cells exhibited dec reased transcriptional template activity with E. coil DNA-dependent RNA pol ymerase.