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Kinetic Analysis of Cell Killing Effect Induced by Cytosine Arabinoside and Cisplatin in Relation to Cell Cycle Phase Specificity in Human Colon Cancer and Chinese Hamster Cells¹

Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Kami-Ikebukuro, Toshima-ku, Tokyo 170 [S. O., J. M., M. I.]; and Faculty of Pharmaceutical Science, University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113 [Y. S.]

We presented a cell kill pharmacodynamic model for cell cycle phasespecific antitumor agents as well as that for cell cycle phase-nonspecific agents. The former was based upon assumptions that a cell population could be divided into a drug-sensitive population having sensitive (or specific) cell cycle phase(s) and a drug-resistant population in resistant cell cycle phases. This model revealed that cell killing action of antitumor agents with sufficient cell cycle phase specificity was time dependent. This time dependence was actually observed with cytosine arabinoside by colony-forming inhibition assays using Chinese hamster V79 cells.

On the other hand, the present analysis indicated that cell killing effects of drugs lacking cell cycle phase specificity are dependent on C x T (concentration-time product). We analyzed cell kill kinetics of cisplatin and showed C x T dependence of cell killing action of the drug using human colon cancer WiDr cells. These results indicate that cell killing action of antitumor agents can be kinetically analyzed in terms of cell cycle phase specificity.

¹ This study was supported in part by Grants-in-Aid for Cancer Research from the Ministry of Education, Science and Culture, and for New Drug Development Research from the Ministry of Health and Welfare, Japan.

² Present address: Department of Pharmacology, School of Medicine, Keio University, Shinano-machi, Shinjuku-ku, Tokyo 160, Japan.

³ To whom requests for reprints should be addressed.

Received 12/15/88. Revised 4/10/89. Accepted 4/19/89.

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