Ehrlich Ascites Tumor as a Tool in the Development of Compounds with Immunomodulatory Properties

• Published in: Immunopharmacology and immunotoxicology Vol. 26; no. 4; pp. 511 - 525
• Main Authors: Queiroz, Mary L. S., Valadares, M. C., Bincoletto, C., Dieamant, G. C.
• Format: Journal Article
• Language: English
• Published: England Informa UK Ltd 2004; Taylor & Francis
• Subjects: Animals; Antineoplastic Agents - pharmacology; Ascitic Fluid - pathology; Bone Marrow Cells - immunology; Bone Marrow Cells - pathology; Carcinoma, Ehrlich Tumor - drug therapy; Carcinoma, Ehrlich Tumor - immunology; Carcinoma, Ehrlich Tumor - pathology; Cell Count; Cell Line, Tumor; CFU-GM; Colony-Forming Units Assay; Development of antitumoral compounds; Drug Design; Ehrlich ascites tumor; Hematopoiesis; Hematopoiesis - drug effects; Hematopoiesis - immunology; Hematopoietic Stem Cells - drug effects; Hematopoietic Stem Cells - immunology; Immunologic Factors - pharmacology; Immunomodulation; Long-term bone marrow culture; Male; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Spleen - immunology; Spleen - pathology
• ISSN: 0892-3973; 1532-2513
• DOI: 10.1081/IPH-200042289

In previous works, we have demonstrated that the myeloprotective properties of several natural and synthetic compounds are partly responsible for their antitumor activity in the Ehrlich ascites tumor (EAT) model. In this work, we present information that may be useful to the study of pharmacological and toxicological properties of compounds that affect the hematological compartment. Clonogenic studies in EAT-inoculated mice demonstrated a rapid decrease in bone marrow CFU-GM, whereas a progressive increase in splenic CFU-GM and cellularity was observed, followed by splenomegaly. Bone marrow cellularity declined on the third day after tumor challenge, returning to normal values thereafter. Serum from EAT-bearing mice produced detectable colony-stimulating activity in vitro. Similar results were observed with the conditioned medium from Ehrlich tumor cell cultures, but not with the cell-free Ehrlich tumor ascitic fluid. Tumor inoculation also resulted in a more striking depletion in the number of non-adherent cells in long-term bone marrow cell cultures (LTBMCs) with no bone marrow stroma formation. We speculate that the physiological alterations induced by the EAT growth can be used to assess the ability of compounds to modulate the hematopoietic response.