The effect of nitrogen mustards on enzymes and tissue metabolism; the effect on tissue metabolism

Nitrogen mustards at a concentration forty times the minimum lethal dose inhibited the respiration of all tissues studied but affected anaerobic glycolysis very little. The inhibiting effect increased with time. The respiration of lymphoid tissue was extremely sensitive to nitrogen mustard, as concentrations below the LD(50) definitely inhibited the respiration of rabbit lymph nodes. In tissue slices nitrogen mustards inhibited the oxidation of pyruvate and of l-amino acids and the utilization of NH(3). A number of synthesis reactions were also inhibited, such as the synthesis of carbohydrate, of creatine, and of urea. When added to growing seeds, nitrogen mustards inhibited their growth. In rats given lethal doses of nitrogen mustards there were found complete inhibition of choline oxidation and strong inhibition of pyruvate oxidation by the kidney and partial inhibition of urea synthesis by the liver. Inhibition of bone marrow respiration by nitrogen mustards was prevented by the addition of choline, and of dimethylaminoethanol plus methionine The possible mechanism of nitrogen mustard intoxication is discussed.