Role of iron in asbestos-body-induced oxidant radical generation.
Asbestos bodies (AB) were harvested from human lung tissue digests and isolated from uncoated asbestos fibers. Samples containing 1000 AB were added to a reactive solution to investigate the ability of AB to oxidize deoxy-D-ribose and generate reactive oxygen species (ROS) in the presence of ascorbate and hydrogen peroxide as determined by formation of thiobarbituric acid (TBA)-reactive products. Three types of asbestos fibers were tested for comparison, since they are known to be able to produce ROS. The absorbance values measured with 1000 AB were significantly higher than those observed with 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 iron derived from the ferritin coating of AB was involved in oxidant generation. Addition of iron to AB enhanced TBA-reactive product formation, while chelation of Fe with deferoxamine reduced this reaction. Hydroxyl radical scavengers 1,3-dimethyl-2-thiourea (DMTU) and mannitol (MN) also effectively blocked TBA-reactive product generation. Data indicate the importance of Fe in AB-induced oxidant damage. With the addition of polymorphonuclear leukocytes (PMN) to AB, incubation in the reactive solution gave very high amounts of TBA-reactive products, but using a reactive solution devoid of ascorbate, very low amounts of TBA-reactive products were generated. In the latter condition, the superoxide of cell membranes probably reduced and removed iron from AB-coating ferritin, but less effectively than ascorbate. Further after the possible reoxidation of Fe2+, Fe3+ could be coordinated by lactoferrin. Since such availability of reductant is never approached in living systems, the iron in the AB coating is unlikely to function as a catalyst of Fenton-type reactions in vivo.
Governa
M
M
Institute of Occupational Health, University of Ancona, Italy.
Amati
M
M
Fontana
S
S
Visona I
Botta
G C
GC
Mollo
F
F
Bellis
D
D
Bo
P
P
D001194:Asbestos / Q000633:toxicity*; D001195:Asbestosis / Q000097:blood / Q000378:metabolism / Q000473:pathology*; D002614:Chelating Agents / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D017665:Hydroxyl Radical / Q000378:metabolism; D066298:In Vitro Techniques; D007501:Iron / Q000502:physiology*; D008855:Microscopy, Electron, Scanning; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D013054:Spectrophotometry, Atomic; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
D002614:Chelating Agents; D005609:Free Radicals; D017392:Thiobarbituric Acid Reactive Substances; D001194:Asbestos; D017665:Hydroxyl Radical; D007501:Iron