The lethal and cytokinetic effects of peptichemio (multipeptide complex of m-[di(2-chloroethyl)amino]-l-phenylalanine), a polypeptide derivative of l-phenylalanine mustard, were investigated on a human lymphoma cell line (T1 cells) by means of colony formation and serial DNA histograms. One hr of exposure of exponentially growing T1 cells to increasing concentrations of peptichemio resulted in a biphasic exponential survival curve. Prolongation of drug treatment effected progressive reduction of D0 to a minimum of 0.25 µg/ml after 12 hr of incubation. One hr of exposure of synchronized cultures to 2.5 µg/ml killed cells in G1 and G2 more effectively than those in S phase. Cell cycle traverse was delayed in S and, more markedly, in G2. These kinetic perturbation effects increased with increasing drug concentrations and incubation times. Treatment of exponentially growing T1 cells with 10 µg/ml for >12 hr caused a largely irreversible S-phase arrest, reducing the degree of G2 accumulation observed after exposure to lower concentrations and/or shorter incubation times. The position of the cells in the cell cycle at the time of drug incubation (5.0 µg/ml, 1 hr) determined the extent and onset of subsequent G2 delay; cells in G1 and early S phase were blocked in the premitotic phase of their immediate lifespan, whereas late S and G2 cells underwent cell division without significant delay and were arrested in the G2 phase of the subsequent generation.
Supported by Contract N01-CM-53773 from the National Cancer Institute, Division of Cancer Treatment, and by Grant CA 14528 from the NIH, USPHS, Bethesda, Md. 20014.