Control of Growth of Mammalian Cells in Culture with Folic Acid, Thymidine, and Purines

SUMMARY Cells cultured directly from various rabbit organs (liver, kid- ney, lung), unlike the permanently cultivatable mammalian cells studied, require relatively large concentrations of folic acid for growth or to attain a maximal rate of growth. The defect in the primary cultures may be related to the reduction of folic acid. Consistent is the observation that 5-formyltetrahydrofolic acid is about 30 times more active than the unreduced vitamins tested. With the liver cells, the folic acid requirement is satisfied by a mixture of thymidme, adenine, and glycine. The rate of growth of the liver cells can be readily manipulated with the vitamin, whereas cell yields can be controlled by the availability of thy- midine and adenine. Contrary to the behavior of bacteria, liver cells incorporate thymidine even under conditions of gratuity. Thymidine cannot be replaced with thymine or with any of the other pyrimidines, purines, and derivatives examined. On the other hand, all the purines and derivatives tested, except guanine, appear to be capable of substituting for adenine.