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In Vitro and in Vivo Studies of the Antileukemic Action of N,N''-bis [p-(N'-methylamidino)phenyl]terephthalamidine, tetrahydrochloride (NSC 57155) on P815 Leukemic Cells¹

Division of Experimental Chemotherapy, Sloan-Kettering Institute for Cancer Research, and Cornell University Medical College, New York, New York

The effect of various concentrations of N,N''-bis[p-(N'-methylamidino)phenyl]terephthalamidine, tetrahydrochloride (NSC 57155)⁴ for various incubation periods on P815Y cells in tissue culture and on sensitive P815 and resistant P815/NSC 57155 cells in mice was studied. A 50% growth inhibition in tissue culture after 72 hr was produced by incubation with 300 µg/ml for 15–30 min, 100 µg/ml for 1–2 hr, or 1 µg/ml for 72 hr.

The incorporation of NSC 57155-¹⁴C into cells and its distribution in nuclei and cytoplasm were studied with a 2-hr incubation at a concentration of 100 µg/ml. After that period most of the activity was found in the cytoplasm and only very little in the cell nuclei. More than 50% of this activity could be extracted with nonpolar solvents.

Incorporation of NSC 57155-¹⁴C occurred at a slower rate in resistant P815/NSC 57155 cells than in sensitive P815 cells.

When P815 and P815/NSC 57155 cells were bioassayed after in vitro incubation with 100 µg/ml of NSC 57155, the cytostatic effect was found to be time dependent. P815/NSC 57155 cells were somewhat sensitive to these high concentrations of the drug, but a longer incubation period was required than with the sensitive cells.

¹ These studies were supported in part by USPHS Research Contract SA-43-ph-2445, Cancer Chemotherapy National Service Center, National Cancer Institute; and Special Research Grant T 45 F from the American Cancer Society, Delaware Division.

⁴ Synthesized by the Research Division of Dr. A. Wander AG, Berne, Switzerland, and supplied by the Cancer Chemotherapy National Service Center of the National Cancer Institute, USPHS.

² Recipient of the Eleanor Roosevelt International Cancer Fellowship through the Union Internationale Contre le Cancer.

³ Permanent Address: Oncological Research Institute, Bratislava, Czechoslovakia.

Received 9/ 2/64. Revised 1/19/66.