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Cytotoxicity in Human Cell Cultures as a Primary Screen for the Detection of Anti-Tumor Agents^*

( Section on Experimental Therapeutics, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda 14, Md.; Laboratories of Microbiology, Children's Cancer Research Foundation, and Department of Pathology, Harvard Medical School, Children's Medical Center, Boston, Mass.)

One hundred and eighty compounds which had been tested in at least three experimental tumors were examined for cytotoxicity against human cell cultures derived from normal and malignant tissue.

1. Confirming previous results, there was no regular difference in the susceptibility of the two cell lines to the various agents.

2. In general, the tumor-active compounds as a group were significantly more cytotoxic than the tumor-inactive compounds. Of the 68 compounds reported to inhibit at least two tumor systems, 54 (79 per cent) were growth-inhibitory in tissue culture at 10^-4 gm/ml, 49 (72 per cent) at 10^-5, and 31 (46 per cent) at 10^-6 gm/ml or less. Of 91 compounds lacking anti-tumor activity, nineteen were cytotoxic at 10^-4, nine at 10^-5, and only two at 10^-6 gm/ml.

3. All eleven compounds which were cytotoxic at 10^-7 gm/ml or less had an anti-tumor effect, and ten of these were active in at least two tumor systems. Of the 37 compounds cytotoxic at 10^-6 gm/ml or less, 35 (95 per cent) were reported to be tumor-active, and 31 (84 per cent) were active in at least two tumor systems.

4. The possible usefulness of tissue culture as a primary screen for candidate anti-tumor agents is discussed.

^* Presented in part at the 48th Annual Meeting, American Association for Cancer Research, Inc., April 12, 1957, Chicago, Illinois.

These studies were supported in part by research grants C-2782 and CY 3335 from the National Cancer Institute, National Institutes of Health, United States Public Health Service.

Received 2/14/58.

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