Intracellular DNA damage produced by a series of diacridines.
The intracellular DNA damage produced by a series of diacridines after a 2 h pulse treatment of L1210 cells in culture was investigated by using the alkaline-elution technique. Like other intercalating agents, diacridines produce single-strand breaks and protein-DNA links. There is a large increase in both types of damage as the alkane chain linking the two 9-aminoacridine residues is increased beyond five methylene groups, which is consistent with the previously observed change from monofunctional to bifunctional intercalation [Wakelin, Romanos, Chen, Glaubiger, Canellakis & Waring (1978) Biochemistry 17, 5057-5063]. For linker chains of less than six methylene groups these agents produce less DNA damage than does the parent 9-aminoacridine at the same drug concentration. Unlike the monofunctional intercalators previously investigated [Ross, Glaubiger & Kohn (1979) Biochim. Biophys. Acta 562, 41-50; Zwelling, Michaels, Erickson, Ungerleider, Nichols & Kohn (1981) Biochemistry 20, 6553-6563; Zwelling, Kerrigan & Michaels (1982) Cancer Res. 42, 2687-2691; Zwelling, Michaels, Kerrigan, Pommier & Kohn (1982) Biochem. Pharmacol. 31, 3261-3267], there is no correlation between the number of single-strand breaks and protein-DNA links produced by these diacridines.
D000166:Acridines / Q000494:pharmacology*; D000468:Alkalies; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002621:Chemistry; D004247:DNA / Q000378:metabolism*; D007364:Intercalating Agents / Q000494:pharmacology*; D007939:Leukemia L1210 / Q000378:metabolism; D046911:Macromolecular Substances; D051379:Mice; D011506:Proteins / Q000378:metabolism
D000166:Acridines; D000468:Alkalies; D007364:Intercalating Agents; D046911:Macromolecular Substances; D011506:Proteins; D004247:DNA