Iron mobilization from crocidolite asbestos by human lung carcinoma cells

Neutron-activated crocidolite, containing 55Fe and 59Fe, was used to determine whether iron was mobilized from crocidolite phagocytized by cultured human lung carcinoma cells (A549 cells). Cells were treated with neutron-activated crocidolite in medium at pH 6.8 or 7.4 for 24 h. The mobilization of iron into two subcellular fractions, 10,000g supernatant (total iron) or < 10,000 MW [low-molecular-weight (LMW)] was monitored using scintillation counting. Iron was mobilized from crocidolite at a rate similar to that observed in vitro when citrate was incubated with crocidolite for 24 h at pH 7.4, but the amount mobilized was greater when cells were cultured at pH 6.8 than at 7.4. Iron mobilization was not due to the medium nor did it appear to be due to differences in the amount of crocidolite phagocytized. At the highest concentration of crocidolite used for treatment at pH 7.4 (4.5 micrograms/cm2), a total of 3600 pmol iron/10(6) cells was mobilized of which 54 pmol/10(6) cells was in a LMW fraction. After estimation of the volume of the cells, this was calculated to be equivalent to an intracellular concentration of 1.4 mM iron of which 22 microM was in the LMW fraction. Cell survival decreased linearly as the iron mobilized into the LMW fraction increased, independent of the pH of the culture medium being used. These results suggest that iron mobilization from crocidolite into a LMW fraction may represent "iron overload" in cells which have phagocytized the fibers and may be responsible for crocidolite-dependent cytotoxicity and possibly other crocidolite-dependent biological effects.