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The Effect of Adriamycin on the Cell Cycle Traverse of a Human Lymphoid Cell Line¹

Departments of Developmental Therapeutics [B. B., E. J F.], Laboratory Medicine [B. D.], and Biomathematics [D. A. J.], The University of Texas System Cancer Center M. D. Anderson Hospital and Tumor Institute, Houston, Texas 77025

The kinetic response of a human lymphoma cell line to adriamycin was analyzed by means of pulse cytophotometry. Depending on concentration and exposure time, cell cycle progression was delayed in G₁, S, and G₂ phases. There was a differential sensitivity for the interaction of adriamycin with the transit through these phases. G₂ arrest could be induced by low concentrations of adriamycin, whereas the block in G₁ was exerted only after long-term treatment with high concentrations and was completely reversible after drug removal. Delay in S-phase transit was transient in spite of continuous exposure to high concentrations of adriamycin. Thus, concentration and duration of treatment determined the magnitude of G₂ arrest as well as onset and rate of G₂ accumulation due to progression delay in G₁ and S phases. Cell age had only little influence on the degree of subsequent G₂ arrest. Irreversibility of the G₂ block strongly suggests eventual cell death in G₂ phase, which may be utilized as a predictive test for response to adriamycin in vivo.

¹ Supported in part by Contract NO1-CM-61156 with the Division of Cancer Treatment, National Cancer Institute.

Received 12/22/75. Accepted 3/ 3/76.

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