Several repair endonucleases were used to characterize and quantify various types of DNA damage induced by 7H-dibenzo[c,g]carbazole (DBC) and its methyl derivative, N-methyldibenzo[c,g]carbazole (MeDBC). Differences in the DNA damage profile induced by these two derivatives were found to be related to their chemical structure and dependent on the way of their metabolic activation. Different ways of activation gave rise to different numbers of single strand breaks and DNA modifications or, at least, to different ratios of common modifications. DBC induced the highest level of breaks in human hepatal cell line Hep G2, while MeDBC induced most of the breaks in V79 cell line with stable expression of human cytochrome P4501A1. Our results support the idea of two different pathways of biotransformation of DBC and MeDBC.
A series of carbocyclic analogues of netropsin were synthesized and evaluated for their capacity to inhibit human topoisomerases I and II in vitro. The compounds are oligopeptides containing 1,4-di- and 1,2,5-trisubstituted benzene rings and unsubstituted N-terminal NH2 groups. Compounds 4-7 consist of two netropsin-like units linked by aliphatic (tetra- and hexamethylene) chains. In the topoisomerase I and II assay, the relaxation of pBR322 plasmid was inhibited by compounds 4-7 at 100 uM concentration.