Inactivation of Amino Acid Transport Systems in Ehrlich Ascites Carcinoma Cells by Cobalt-60 Gamma Radiation

Suspensions of Ehrlich ascites cells were subjected to doses up to 8.27 × 10⁵ rads of γ-radiation from a⁶⁰ Co source. Initial rates of uptake of α-aminoisobutyric acid (AIB) and L-serine by the A route of entry (dependent on energy and the Na⁺ gradient and inhibited by α-(methylamino)-isobutyric acid (MeAIB)), of L-serine by the ASC route (dependent on energy and the Na⁺ gradient, but not inhibited by MeAIB), and of L-phenylalanine by the L component (independent of energy and the Na⁺ gradient, not inhibited by lysine) and by the${\rm L}^{0,+}$ component (similar to L, but inhibited by lysine) were measured. Uptake by the A and ASC transport systems was more radiosensitive than was uptake by the L and${\rm L}^{0,+}$ components. Cells irradiated in Na⁺-free buffer showed marked losses of intracellular K⁺ and slight losses of intracellular Na⁺; cells irradiated in buffer containing 143 mN Na⁺ apparently lost K⁺ but gained Na⁺ markedly. Values of$D_{37}$ found were 2.5× 10⁵ rads for uptake of amino acids by the A system, identical values for the ASC system, and 4.5× 10⁵ rads for K⁺ retention. The effectiveness of inhibition by γ-radiation of the membrane functions studied was inversely related to the concentration of cells irradiated. It is suggested that γ-radiation inactivates the A and ASC amino acid transport systems and K⁺ entry by indirect action on components of these systems in the membrane, perhaps disassociating the systems from cellular energy, and that very high doses cause structural disorientation in the membrane.