Unusual dynamics of killing of cultured lewis lung cells by the DNA-intercalating antitumour agentN-[2-(dimethylamino)ethyl]acridine-4-carboxamide

Abstract

The cytotoxicity ofN-[2-(dimethylamino)ethyl]acridine-4-carboxamide (AC; NSC 601 316), a new experimental DNA-intercalating antitumour drug, against a cultured Lewis lung adenocarcinoma cell line was compared with that of the DNA-intercalating antitumour drug amsacrine. In contrast to amsacrine, AC demonstrated self-inhibition of cytotoxicity following short (3–9 h) incubation periods and exponential killing (with a shoulder) after long (24–72 h) periods of incubation. The difference between these drugs was best demonstrated using a constant concentration x time (CxT) exposure (AC, 12 μmol h l⁻¹; amsacrine, 3 μmol h l⁻¹). In contrast to amsacrine, AC was minimally effective over exposure periods of ≤1 h and maximally effective over intermediate periods (4–6 h). The results suggest the possibility of designing AC administration protocols that maximise the drug's cytotoxicity towards solid tumours, which, because of diffusion barriers, are subjected to longer drug exposures than are well-vascularised tumours.