IRON MOBILIZATION FROM CROCIDOLITE ASBESTOS BY HUMAN LUNG-CARCINOMA CELLS

Neutron-activated crocidolite, containing Fe-55 and Fe-59, 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, 10,000 g su pernatant (total iron) or < 10,000 MW [low-molecular-weight (LMW)] was monitored using scintillation counting. Iron was mobilized from croci dolite at a rate similar to that observed in vitro when citrate was in cubated 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 mobil ization was not due to the medium nor did it appear to be due to diffe rences in the amount of crocidolite phagocytized. At the highest conce ntration of crocidolite used for treatment at pH 7.4 (4.5 mu g/cm(2)), 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 t he cells, this was calculated to be equivalent to an intracellular con centration of 1.4 mM iron of which 22 mu M was in the LMW fraction. Ce ll survival decreased linearly as the iron mobilized into the LMW frac tion 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 phag ocytized the fibers and may be responsible for crocidolite-dependent c ytotoxicity and possibly other crocidolite-dependent biological effect s. (C) 1994 Academic Press, Inc.