An electron microscopical and histochemical study on ferric nitrilotriacetate-induced "F1 amyloidosis".

Of a total of 80 offspring obtained by reciprocal crossing of ICR/JCL strain of mice of both sexes receiving 84-140 injections of Fe-NTA over 98-163 days before crossing, 52 (65%) showed severe generalized amyloidosis after 93-502 injections of Fe-NTA over 115-522 days, but not "hemochromatosis", which was a striking contrast to the findings of "hemochromatosis" without amyloidosis observed in the parent mice. Electron microscopic examinations revealed numerous bundles of non-branching, well-oriented amyloid fibrils radiated outward from the surface of cytoplasmic invaginations of the Kupffer cells or splenic reticuloendothelial cells of the F1 mice with amyloidosis, and close contact frequently observed between "amyloid-forming cells" and adjacent lymphocytes in the amyloid-laden liver and spleen of the F1 mice. Since the above findings in the F1 mice were not found in the parent mice treated with multiple Fe-NTA injections, the present authors assumed that the immunological memory for the Fe-NTA conjugate transmitted via the placenta to the fetus from the mother that received multiple Fe-NTA injections might be involved in the development of generalized amyloidosis in the F1 mice, although the possible mechanism by which Fe-NTA-induced "F1 amyloidosis" has been developed remains yet undetermined.