Electrophoretic and Morphologic Studies of a Transplantable Reticulum-Cell Neoplasm in Mice Inducing Amyloidosis2

Abstract

The first 10 transfer generations of a reticulum-cell neoplasm of the mouse constantly associated with the development of amyloidosis are described. Microscopic examination revealed that the grafts were pyroninophilic, plasma-cell differentiated reticulum-cell sarcomas, spreading diffusely, especially to the lymph nodes, liver, and spleen. Serum-protein changes observed in paper electrophoresis and immuno-electrophoresis were a hypergamma-globulinemia changing to an increase in the β- (β₂-_III) and α₂-fractions (α_2-I and _2-II) and eventually to a reduction in albumin and β-globulin and a further increase in the α₂-fraction (α_2-III and _2-V); the latter changes were accompanied by urinary excretion, particularly of albumin and β-globulin (β_2-I). During tumor growth a relative and often an absolute granulocytosis and monocytosis were seen. Amyloid development first was found, most frequently and markedly, in the spleen, then in the liver, in the kidneys, and, occasionally, in many other organs. Mice with the longest survival time showed the heaviest degree of amyloidosis. Our findings indicated that amyloidosis was due to a persistent hyperimmunization, in accordance with the theory of the pathogenesis of amyloidosis advanced by Teilum. The last stage of the serum-protein changes and the urinary elimination of protein were explained as caused by the development of a nephrotic syndrome caused by renal amyloidosis. In mice with a short survival time and extensive tumor growth without amyloidosis, a paraprotein-like γ-protein was found in serum and the tumors showed a more plasma-cell differentiated picture.