Effects of New Antitumor Bifunctional Intercalators Derived from 7H-Pyridocarbazole on Sensitive and Resistant L1210 Cells

摘要: Abstract The antitumor properties of 7 H -pyridocarbazole dimers, a new series bifunctional intercalators, have recently been described (Pelaprat, D., Delbarre, A., Le Guen, I., Roques, B. P., and Pecq, J. Med. Chem., 23: 1336–1343, 1980; Pelaprat, Porcher, G., Gosse, C., Biochem. Pharmacol., 28: 1811–1815, 1979). In order to study the mechanism action these compounds, an L1210 subline was made resistant one dimer (NSC 335153; ditercalinium). Selection cells based on in vitro-in vivo procedure as follows. Ascitic were taken from leukemic mouse incubated vitro with for 1 hr. They then injected into mice. After development ascites, collected process repeated 13 times, until establishment resistance. Cloned maintained their resistance 18 months culture. effects two dimers 335153 NSC 335154) cell viability, growth, colony formation, cycle progression investigated parental cells. cross-resistance lines several cytotoxic agents estimated. Several observations indicate that might be different monointercalating agents: ( ) drugs induce delayed toxicity (growth arrest occurring five generations after drug exposure) sensitive but not cells; b exposed arrested almost randomly all phases cycle, whereas corresponding monomer provokes block G 2 + M phase. Resistant cross-resistant monomer, Adriamycin, vincristine 6 derivatives, actinomycin D, methotrexate.