leupeptins and Leukemia--Lymphoid

Lymphocytes from normal human subjects and from patients with chronic lymphocytic leukemia were found to degrade their endogenous protein at similar rates (2.5-3.0%/h) when incubated in an amino acid-free buffer. Protein degradation was inhibited 20-35% by inhibitors of autophagic sequestration (amino acids, 3-methyladenine) and by inhibitors of intra-lysosomal proteolysis (leupeptin, propylamine), the extent of inhibition being similar in normal and leukemic lymphocytes. The inhibitor effects, together with the electronmicroscopic demonstration of autophagosomes in the lymphocyte cytoplasm, is taken as evidence for the existence of an autophagic-lysosomal pathway in human lymphocytes, potentially responsible for as much as one-third of their overall protein degradation.

Topics: Adenine; Amino Acids; Autophagy; Humans; Leukemia, Lymphoid; Leupeptins; Lymphocytes; Lysosomes; Neoplasm Proteins; Phagocytosis; Propylamines; Proteins

The effect of leupeptin on the induction of lymphoblastic leukemia in ICR/JCL female mice by N-nitrosobutylurea (NBU) was investigated. NBU was given as a 0.02% solution in drinking water for 10 weeks. A 0.1% concentration of leupeptin was given in the diet. Group A was fed on the leupeptin diet from the beginning, Group B received it after the end of NBU treatment, and Group C was fed on a leupeptin-free control diet throughout. The average periods in the appearance of leukemia in groups A, B, and C were 115+/-50, 112+/-43, and 100+/-17 days (mean+/-SD), respectively, and there was a significant difference between groups A and B and Group C at P less than 0.001. In regard to this point, leupeptin might have the effect of retarding the rpocess of leukemogenesis. However, leupeptin showed no effect on the incidence and histopathological finding of leukemia.

Topics: Animals; Body Weight; Female; Leukemia, Experimental; Leukemia, Lymphoid; Leupeptins; Mice; Mice, Inbred ICR; Nitrosourea Compounds; Oligopeptides; Thymus Gland; Thymus Neoplasms