Effects of wheat germ agglutinin on membrane transport

1. (1) Low concentrations of wheat germ agglutinin are cytotoxic toward several tissue culture lines, including Chinese hamster ovary cells, Swiss 3T3 cells, mouse L cells and baby hamster kidney cells. The LD₅₀ ranged from 1 to 5 μg wheat germ agglutinin per ml. Similar concentrations of the lectin inhibited the transport of the non-utilizable amino acids α-aminoisobutyric acid and cyclo-leucine and inhibited the uptake of thymidine. In contrast, 2-deoxy-d-glucose uptake was not altered and colchicine uptake was enhanced. 2. (2) The inhibition of α-aminoisobutyric acid uptake occurred within minutes after lectin addition and was maximal by 1 h. Maximal inhibition ranged from 50 to 70% of control values. Studies of the kinetics of the uptake demonstrated that wheat germ agglutinin decreased the V of the uptake by 70% without affecting the apparent K_m. Ovomucoid, a haptene inhibitor of wheat germ agglutinin-binding to cell surface receptors, prevented the wheat germ agglutinin-induced inhibition of α-aminoisobutyric acid transport. Three other lectins (Concanavalin A, Phaseols vulgaris E-phytohemagglutinin and l-phytohemagglutinin) inhibited the uptake by 20% or less at doses up to 50 μg/ml. 3. (3) We propose that the cytotoxicity of wheat germ agglutinin probably results in part, if not totally, from membrane alterations which impair multiple membrane transport systems.