Effects of 7H-pyridocarbazole mono and bifunctional DNA-intercalators on chinese hamster lung cells in vitro

Abstract The effects of two 7 H -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 G 2 + M phase; after a transitory exposure to either one of the dimers, the cell growth arrest was delayed for 6–8 generations. Therefore, the 7 H -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.