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In Vitro Cytokinetic Response of Human Colon Cancer Cells to cis-Dichlorodiammineplatinum(II)¹

Departments of Developmental Therapeutics [J-P. B., B. B., W. G.], Biomathematics [D. A. J.], and Laboratory Medicine [B. D.], The University of Texas System Cancer Center, M. D. Anderson Hospital and Tumor Institute, Houston, Texas 77030

The cytokinetic response of a human colon carcinoma cell line to cis-dichlorodiammineplatinum(II) was investigated using flow cytometry of DNA content, autoradiography after pulse and continuous tritiated thymidine exposure, and mitotic accumulation after continuous Colcemid treatment. With increasing concentration and exposure time, cis-dichlorodiammineplatinum(II) delayed and then blocked cycle traverse in S and G₂ phases. After prolonged treatment with high concentrations of cis-dichlorodiammineplatinum(II), an additional block in G₁ or at the G₁-S boundary was established. Irreversibility of cell cycle distribution changes after prolonged observation periods suggests cell death in G₂, S, and G₁ compartments.

¹ Supported in part by Grants CA-14528 and CA-23272 from the National Cancer Institute, NIH, Bethesda, Md. 20205.

² Supported by a grant from the Lilly International Fellowship Program, Indianapolis, Ind. 46206.

³ Junior Faculty Fellow of the American Cancer Society. To whom requests for reprints should be addressed, at Department of Developmental Therapeutics, The University of Texas System Cancer Center, M. D. Anderson Hospital and Tumor Institute, 6723 Bertner, Houston, Texas 77030.

Received 1/16/79. Accepted 7/30/79.