A tissue culture cytotoxicity test for large-scale cancer chemotherapy screening.

Recent reviews of the role of tissue culture in cancer chemotherapy screening (5, 6) have emphasized the need for a more extensive trial of cell cultures as a screening tool for the detection of anti-tumor substances. Eagle and Foley (~--4) have reported the cytotoxic activity against human cell cultures of more than 180 selected compounds. These compounds had previously been tested against at least three experimental animal tumors. I t was found that 79 per cent of the substances active against two or more experimental tumors showed cell culture act ivity at 10 -4 gm/ml or less. This degree of sensit ivi ty was achieved at the cost of ~1 per cent of the tumor-negative compounds also exhibiting cell culture activity at the arbitrary cut-off point of 10 --4 gm/ml or less. I t was also observed that there was no regular difference in the susceptibility to the various drugs of the cell lines derived from malignant and normal tissue. Eagle and Foley concluded that a large-scale investigation of the usefulness of human cell cultures as a cancer chemotherapy screening procedure was warranted. Ni t ta (7-9) has tested 38 antibiotics and synthetics of varying anti-tumor activity against HeLa cell cultures. I t was found that, in general, the strong tumor-inhibitory antibiotics were destructive to HeLa cells at the lowest concentrations, while those antibiotics inactive against animal tumors were least injurious to the cell cultures. Ni t ta concluded that the test method with the use of HeLa cells can be practically applied to the screening or assay of the anti-tumor activity of substances. The large-scale screening program of the Cancer Chemotherapy National Service Center (CCNSC) with experimental animal tumors affords a unique opportunity to test concomitantly the reliability