Effects of 7H-pyridocarbazole mono and bifunctional DNA-intercalators on Chinese hamster lung cells in vitro.
The effects of two 7H-pyridocarbazole dimers, PyDi1 and PyDi2, on Chinese hamster lung cells in culture in vitro, were compared to those of the corresponding monomers, PyMo1 and PyMo2, by measuring the rates of macromolecule syntheses, the growth kinetics of the drug-treated cells, and the cell cycle progression. The dimers, which are endowed with a very high DNA affinity, were about 10- and 40-fold more cytotoxic than the monomers from which they markedly differ in the following ways: in contrast to monomers, the dimers do not provoke the arrest of cell cycle progression in the G2 + M phase; after a transitory exposure to either one of the dimers, the cell growth arrest was delayed for 6-8 generations. Therefore, the 7H-pyridocarbazole dimers express their cytotoxicity through a mechanism of action different from that of their mono-intercalating counterparts. They might then constitute a new series of antitumour drugs.
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000378:metabolism*; D004261:DNA Replication / Q000187:drug effects; D004611:Ellipticines / Q000494:pharmacology*; D007364:Intercalating Agents / Q000494:pharmacology*; D007700:Kinetics; D008168:Lung; D014176:Protein Biosynthesis / Q000187:drug effects; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic / Q000187:drug effects
D000470:Alkaloids; D004611:Ellipticines; D007364:Intercalating Agents; D004247:DNA