Glutamine and the regulation of DNA replication and cell multiplication in fibroblasts

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Abstract
Several studies indicate that glutamine is a critical requirement for cell growth in vitro. Growing and quiescent (serum‐starved) 3T3‐fibroblasts were exposed to media (Dulbecco's modified Eagle's minimal essential medium) in which the concentration of the 13 essential amino acids had been lowered to 1/100 or 1/1,000 of that in DMEM ‐ either all together or one by one. The effects on DNA synthesis were measured by autoradiographic determinations of the percentage of labeled cells after 24 hours exposure to 3H‐thymidine. A reduction of all 13 essential amino acids to 1/100 or 1/1,000 of the normal concentration in the medium resulted only in a minor growth inhibitory effect during the first cell cycle. A similar growth inhibitory effect was caused by the depletion of one of the 13 essential amino acids (except glutamine) from the medium. However, a depletion of glutamine from the medium resulted in a marked inhibition of growth. Conversely, a relative excess of glutamine, when the other 12 amino acids were lowered to 1/1,000 of the normal concentration, counteracted the growth inhibitory effect of serum starvation. It was even possible to stimulate quiescent cells to undergo DNA synthesis by exposing them to a serum‐depleted (0.5% serum) medium with a relative excess of glutamine.