Prevention of oncogenic viral infections in mice with CGP 11637, a synthetic muramyl dipeptide analog.
The efficacy of N-acetyl-nor-muramyl-L-alanyl-D-isoglutamine (nor-MDP) in controlling viral oncogenesis in mice was investigated. The tumors studied were blood cell malignancies induced by Friend leukemia virus in SJL/J mice, spontaneous mammary neoplasms in RIII/Imr and C3H/OuJ mice, and spontaneous lymphocytic leukemia in AKR/J mice. A transplantable tumor, Lewis lung carcinoma, in C57BL/6J mice was used as a nonvirally induced control model. The nor-MDP was dissolved in saline and made into an emulsion with an equal volume of squalene-Arlacel A and injected subcutaneously at 1- to 2-month intervals. Test and control mice were challenged with exogenous virus or tumor transplant 2 weeks after a second injection of nor-MDP. Administration was started at around 2 months of age in mice that develop spontaneous neoplasms. Electron microscopy studies were done on neoplastic tissues of selected test and control mice. This administration of nor-MDP prevented erythroleukemia in SJL/J mice caused by low doses of Friend leukemia virus (although erythroleukemia survivors were not protected from a late-developing lymphoma) and also delayed (possibly prevented) the development of a spontaneous mammary neoplasm in RIII/Imr mice. No antitumor effects were observed on the spontaneous neoplasms of C3H/OuJ and AKR/J mice or on the Lewis lung carcinoma implanted into C57BL/6J mice. Electron microscopic examinations of the various neoplastic tissues indicated that nor-MDP administration eliminated or reduced extracellular viruses. The results suggested that under the experimental conditions used nor-MDP appears to effect the viruses and not the malignant cells per se.
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D005622:Friend murine leukemia virus; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology / Q000517:prevention & control; D007942:Leukemia, Experimental / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000473:pathology / Q000517:prevention & control; D051379:Mice; D008815:Mice, Inbred Strains; D009374:Neoplasms, Experimental / Q000473:pathology / Q000517:prevention & control; D013154:Spleen / Q000648:ultrastructure; D013950:Thymus Gland / Q000648:ultrastructure; D014412:Tumor Virus Infections / Q000473:pathology / Q000517:prevention & control*
D000998:Antiviral Agents; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C047676:N-acetyl-nor-muramyl-L-alanyl-D-isoglutamine