vitamin-b-12 and Leukemia-P388

The effect of cobalamin (vitamin B12) on the survival time of mice bearing P388 leukemia has been examined. Among the three cobalamins studied, the enzymatically active derivatives, methylcobalamin and 5'-deoxyadenosylcobalamin, were able to significantly increase the survival time of mice implanted intraperitoneally with the tumor cells. The pharmaceutical form, cyanocobalamin, was not active. The antitumor activity of these cobalamins may be associated with their functions in metabolism.

Topics: Animals; Body Weight; Cobamides; Female; Lethal Dose 50; Leukemia P388; Mice; Mice, Inbred DBA; Mice, Inbred Strains; Structure-Activity Relationship; Vitamin B 12

Cobalamin-deficient P388D1 mouse leukemic cells were created by propagation in a cyanocobalamin-free medium in which the original fetal bovine serum was replaced by bovine serum albumin. These cobalamin-deficient cells gradually ceased to multiply when the medium contained 5-methyltetrahydrofolate. The growth of cells that had been cultured with this coenzyme was recovered following the addition of cyanocobalamin (CNCbl), at concentrations above 37 pM. In contrast to the effect of CNCbl, cobinamide, and cobalamin analogues prepared from hydroxy cobalamin by reaction with ascorbic acid, did not have a growth-inducing effect on these cells, nor did these analogues inhibit CNCbl-dependent growth. Transcobalamin II-cobalamin complex had a remarkably stimulating effect on cell growth. The growth inducing effect became apparent with a cobalamin concentration of only 0.37 pM. This was about 1/100th the level of free cobalamin required for cell growth. However, no growth-inducing effect was seen at an R protein-bound cobalamin concentration of 37 pM, indicating that once cobalamin has been bound to R protein, it loses its growth-promoting effect on these cells in culture.

Topics: Animals; Cell Division; Leukemia P388; Mice; Transcobalamins; Tumor Cells, Cultured; Vitamin B 12

Topics: Animals; Ascorbic Acid; Carcinoma, Ehrlich Tumor; Drug Therapy, Combination; Leukemia P388; Leukemia, Experimental; Mice; Mice, Inbred Strains; Vitamin B 12