DNA damage and cytotoxicity of nitracrine in cultured HeLa cells.
The effects of nitracrine (1-nitro-9-(3,3-N,N-dimethylaminopropylamino)acridine on DNA of cultured HeLa cells were studied. DNA strand breakage and interstrand cross-linking as well as DNA-protein cross-linking were measured by means of an alkaline elution technique and were compared with the cytotoxic effect of the drug. Interstrand cross-links were not detectable in the concentration range that inhibited cell growth up to 99%. DNA single-strand breaks were found when cells were treated with highly cytotoxic doses of the drug. DNA breakage was not reparable and exhibited a tendency to increase during incubation after drug removal. The only chromatin lesion induced by sublethal doses of nitracrine were DNA-protein cross-links which persisted for 24 h after drug treatment. It is concluded that DNA breaks represent degraded DNA from dying cells, whereas DNA-protein cross-links are specific cellular lesions, which may be responsible for the cell-killing effect of nitracrine.
Szmigiero
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L
Department of General Chemistry, Institute of Physiology and Biochemistry, School of Medicine in Lódz, Poland.
Studzian
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K
D000609:Aminoacridines / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects*; D003432:Cross-Linking Reagents; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D006367:HeLa Cells; D006801:Humans; D009564:Nitracrine / Q000633:toxicity*; D011506:Proteins / Q000378:metabolism
D000609:Aminoacridines; D003432:Cross-Linking Reagents; D011506:Proteins; D009564:Nitracrine; D004247:DNA