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Lethal and Kinetic Effects of Peptichemio on Cultured Human Lymphoma Cells¹

Departments of Developmental Therapeutics [B. B., G. P. B.] and Laboratory Medicine [B. D.], The University of Texas System Cancer Center, M. D. Anderson Hospital and Tumor Institute, Houston, Texas 77030, and Fachklinik Hornheide, University of MÜnster Medical School, Münster, Germany [W. G.]

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.

¹ 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.

Received 2/10/77. Accepted 5/ 6/77.