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Antiproliferative Agents and Differential Survival between Normal and Cancer Cells¹

Department of Pediatrics, Section of Developmental Medicine, Stanford University, Stanford, California 94305

A basic difference in response between normal cells (primate fibroblasts) and colonic cancer cells (human and rodent) to the antiproliferative action of both N-(phosphonacetyl)-L-aspartate and thymidine is described in this report. Both normal and colonic cancer cells, when cultured in the presence of these agents, cease to increase their cell numbers. Evidence is presented to show that the normal cells respond to deprivation of pyrimidine nucleotide induced by these agents by simple growth arrest, in which a quiescent state may be maintained for prolonged periods without cell death. Cancer cells are shown to respond in a characteristically different manner in which cell division continues accompanied by limited cell survival, with the surviving population representing a balance of these opposing processes. The extent to which these in vitro findings, based on a limited number of comparisons under restrictive artificial conditions, relate to the in vivo state remains to be established.

¹ This work was supported by USPHS Grants CA 14917, administered through The National Large Bowel Cancer Project, HD 00391, and Training Grant HD00049.

² To whom requests for reprints should be addressed.

³ USPHS Postdoctoral Fellow HD00049.

Received 6/26/78. Accepted 8/16/78.