Crosslinking of cellular DNA by nitracrine and furocoumarin derivatives
Studzian, K.; Tołwińska-Stańczyk, Z.; Wilmańska, D.; Palumbo, M.; Gniazdowski, M.
Neoplasma 46(1): 50-53
1999
ISSN/ISBN: 0028-2685 PMID: 10355534 Document Number: 507457
The anticancer drug, nitracrine, a 1-nitro-9-aminoalkyl derivative of acridine exhibits potent cytotoxic effects which are due to its metabolic activation, 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 compared with furocoumarins of different DNA crosslinking potencies. The existence of crosslinks in DNA upon incubation of cells with nitracrine (1-4 microM) have been confirmed with two different methods under the conditions where 8-methoxypsoralen, a classic crosslinking agent induced the renaturation. The DNA preparation isolated from the drug pretreated cells exhibited decreased transcriptional template activity with E. coli DNA-dependent RNA polymerase.