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Modulation of murine lymphoma growth by n acetylmuramyl l alanyl d iso glutamine n acetylmuramyl d alanyl d glutamine and cyclo phosphamide 1. inhibition of growth in vivo



Modulation of murine lymphoma growth by n acetylmuramyl l alanyl d iso glutamine n acetylmuramyl d alanyl d glutamine and cyclo phosphamide 1. inhibition of growth in vivo



International Journal of Immunopharmacology 5(3): 219-228



The effect of 2 muramyl dipeptides, N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) and N-acetylmuramyl-D-alanyl-D-isoglutamine (MDP(D-D)), on murine lymphoma growth was studied. MDP, administered i.p., inhibited the ascitic growth of 4 of 5 thymoma cell lines expressing either Ly-1+2+ or Ly-1-2+ phenotypes. The growth of a thymoma cell line expressing the Lyt-1+2- phenotype was not inhibited at doses which inhibited the other thymoma cell lines. MDP(D-D) has no significant effect on the growth of the thymoma cell lines, but, in contrast to MDP, significantly inhibited the growth of an Abelson virus-transformed B-cell line and of a plasmacytoma cell line. Cytotoxicity studies indicated that the 2 muramyl dipeptides were not acting in a short-term direct manner on the cells. Comparative studies showed that where the growth of a cell line was inhibited, the 2 muramyl dipeptides were some 7- to 20-fold more effective than cyclophosphamide on a dose/activity basis. The ability of MDP to inhibit the growth of the thymoma cell lines appeared to correlate with their reported levels of terminal deoxynucleotide transferase activity (TdT) rather than with their Lyt-phenotype. MDP, but not MDP(D-D), inhibited those thymoma cell lines having high levels of TdT activity, indicating an effect on cell lines representative of immature T-lymphocytes. The inhibition of the growth of the B-cell and plasmacytoma cell lines by MDP(D-D), an adjuvant-inactive non-pyrogenic stereoisomer of MDP, but not MDP, suggests the existence of a differential specificity of thse 2 muramyl dipeptides for lymphomas of T- and B-lymphocyte origin.

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