ABSTRACT
PURPOSE: To compare the toxicity of lanthanides (cerium, gadolinium) with actinides (thorium, neptunium, uranium) added in soluble form to rat alveolar macrophage cultures. MATERIALS AND METHODS: The metals were added 1 day after seeding alveolar macrophages extracted by pulmonary lavage, and the metal toxicity was scored 3 days later. Cell death was measured after vital staining to distinguish between apoptosis and necrosis; relative cell density was also quantified. The physico-chemical form of the metals in the culture medium was characterized using filtration and radioactive measurements. RESULTS: Except for thorium, induction of cell death was observed for all the elements studied and the death mechanism involved was apoptosis. Graduated toxicity was observed from uranium to neptunium, cerium and gadolinium, in the range of concentration from 10(-3)-10(-6) M. From pilot experiments, it was hypothesized that soluble compounds were mainly involved in lanthanide toxicity, whereas insoluble forms were mainly involved in actinide toxicity. CONCLUSION: This study demonstrates that the toxicity of neptunium and uranium was concomitant with the presence of insoluble forms in the culture medium. Further studies are needed to characterize the cell death mechanisms involved and the potential synergistic effects of chemical toxicity and irradiation.
