Role of iron in asbestos-body-induced oxidant radical generation

Asbestos bodies (AB) were harvested from human lung tissue digests and isol ated from uncoated asbestos fibers. Samples containing 1000 AB were added t o a reactive solution to investigate the ability of AB to oxidize deoxy-D-r ibose and generate reactive oxygen species (ROS) in the presence of ascorba te and hydrogen peroxide as determined by formation of thiobarbituric acid (TBA)-reactive products. Three types of asbestos fibers were tested for com parison, since they are known to be able to produce ROS. The absorbance val ues measured with 1000 AB were significantly higher than those observed wit h 1000 fibers of the three types of asbestos. Since in our reaction system the only source of transition metals was the iron-rich AB, data suggest iro n derived from the ferritin coating of AB was involved in oxidant generatio n. Addition of iron to AB enhanced TEA-reactive product formation, while ch elation of Fe with deferoxamine reduced this reaction. Hydroxyl radical sca vengers 1,3-dimethyl-2-thourea (DMTU) and mannitol (MN) also effectively bl ocked TEA-reactive product generation. Data indicate the importance of Fe i n AB-induced oxidant damage. With the addition of polymorphonuclear leukocy tes (PMN) to AB, incubation in the reactive solution gave very high amounts of TEA-reactive products, but using a reactive solution devoid of ascorbat e, very low amounts of TBA-reactive products were generated. in the latter condition, the superoxide of cell membranes probably reduced and removed ir on from AB-coating ferritin, but less effectively than ascorbate. Further a fter the possible reoxidation of Fe2+, Fe3+ could be coordinated by lactofe rrin. Since such availability of reductant is never approached in living sy stems, the iron in the AB coating is unlikely to function as a catalyst of Fenton-type reactions in vivo.