Effect of long-term removal of iron from asbestos by desferrioxamine B on subsequent mobilization by other chelators and induction of DNA single-strand breaks.
The long-term removal of iron from crocidolite or amosite by desferrioxamine B (DF) at pH 7.5 or 5.0 was studied. Crocidolite or amosite (1 mg/ml) was suspended in 50 mM NaCl at pH 7.5 or 5.0 with the addition of 1 mM DF for up to 90 days. Although the rate of iron mobilization decreased with time, iron was continuously mobilized from both forms of asbestos at pH 5.0 or 7.5. The amount of iron mobilized from crocidolite was at least twice that mobilized from amosite at either pH. Iron was mobilized more rapidly from crocidolite at pH 5.0 than at 7.5 for the first 15 days, but at later times the amount being mobilized at pH 7.5 became equal to or slightly greater than that at 5.0. For amosite, the mobilization at pH 5.0 was always greater than that at pH 7.5. Next, the effect of iron removal from asbestos by DF on subsequent iron mobilization by a second chelator (EDTA or citrate) and on induction of DNA single-strand breaks (SSBs) was studied. Asbestos, treated for up to 15 days with DF at pH 7.5, was washed to remove ferrioxamine and excess DF, then incubated with EDTA or citrate (1 mM). The rates of iron mobilization from both forms of asbestos by a second chelator decreased as more and more iron was removed by DF. Induction of DNA SSBs also decreased, reflecting the unavailability of iron to catalyze the damage. The results suggest three things. First, if long-term mobilization of iron from asbestos occurs in vivo as has been observed in vitro, it may play a role in the long-term biological effects of asbestos. Second, more rapid mobilization of iron from asbestos fibers may occur when the fibers are phagocytized by cells and maintained in phagosomes where the pH is 4.0-5.0. Third, treatment of asbestos by iron chelators, such as DF, prior to exposure to cultured cells or whole animals, may reduce the biological effects of asbestos resulting from iron, but may not completely eliminate them.
Chao
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Department of Chemistry and Biochemistry, Utah State University, Logan 84322-0300.
Aust
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D017639:Asbestos, Amosite / Q000737:chemistry / Q000633:toxicity*; D017638:Asbestos, Crocidolite / Q000737:chemistry / Q000633:toxicity*; D002951:Citrates; D019343:Citric Acid; D004249:DNA Damage; D004277:DNA, Single-Stranded / Q000187:drug effects*; D003676:Deferoxamine; D004492:Edetic Acid; D006863:Hydrogen-Ion Concentration; D007501:Iron / Q000302:isolation & purification / Q000633:toxicity*; D007502:Iron Chelating Agents; D007700:Kinetics; D013997:Time Factors
D002951:Citrates; D004277:DNA, Single-Stranded; D007502:Iron Chelating Agents; D017638:Asbestos, Crocidolite; D017639:Asbestos, Amosite; D019343:Citric Acid; D004492:Edetic Acid; D007501:Iron; D003676:Deferoxamine