Quantitative studies of amino acid and growth factor requirements of transformed and nontransformed cells in high concentrations of serum or lymph.

The growth rate of spontaneously transformed BALB/3T3 cells is proportional to glutamine concentration between 50 and 400 microM, with little or no growth occurring in less than 50 microM glutamine. By contrast, nontransformed BALB/3T3 cells multiply, although slowly, with as little as 20 microM glutamine. Neither cell type depletes the medium of glutamine at the low concentrations. Cystine requirements of both cell types increase with serum concentration, probably due to the binding of half-cystine residues by the serum. Calf serum is a much more potent stimulator of cell multiplication than calf lymph, especially for the nontransformed cells. The rate of cell multiplication can be reduced by lowering the concentration of essential amino acids to the physiologic level found in body fluids, but the growth limitations can be fully compensated by simply raising the serum concentration. Growth factors may act by enhancing the utilization of amino acids, particularly of glutamine which is a required substrate for the first and chief regulatory steps of purine and pyrimidine synthesis. Lymph, which is coextensive with interstitial fluid in vivo, is poor in growth factors for the nontransformed BALB/3T3 cells as well as for recently explanted mouse embryo cells, which raises questions of how normal cell growth is maintained in the body.