DNA strand breaks following in vitro exposure to asbestos increase with surface-complexed [Fe3+].
Surface functional groups on silicate dusts complex iron cations which can cycle through reduction and oxidation states to generate free radicals. These oxidants have a capacity to produce DNA strand breaks and mutations which are primary events in cancer induction. A differential in the capacity of fibrous silicates to produce carcinoma is recognized with the amphiboles demonstrating a greater biologic effect than the serpentine fiber chrysotile. We tested the hypothesis that the differences in genotoxicity of these fibrous silicates correspond to varying concentrations of iron complexed to the surface. Relative to chrysotile, the amphibole fibers complexed greater amounts of iron cations from both inorganic and in vivo sources. Increased concentrations of surface-complexed iron were associated with greater oxidant generation, measured as thiobarbituric acid-reactive products of deoxyribose, and more covalently closed, circular DNA strand scission. These results indicate that genotoxic effects of these fibers may correspond to their capacity to complex iron at the surface.
Ghio
A J
AJ
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
Kennedy
T P
TP
Stonehuerner
J G
JG
Crumbliss
A L
AL
Hoidal
J R
JR
D001194:Asbestos / Q000494:pharmacology*; D017639:Asbestos, Amosite / Q000737:chemistry / Q000494:pharmacology; D017638:Asbestos, Crocidolite / Q000737:chemistry / Q000494:pharmacology; D017632:Asbestos, Serpentine / Q000737:chemistry / Q000494:pharmacology; D004249:DNA Damage / Q000187:drug effects*; D003855:Deoxyribose / Q000378:metabolism; D005290:Ferric Compounds / Q000494:pharmacology*; D010084:Oxidation-Reduction; D013499:Surface Properties; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D017632:Asbestos, Serpentine; D005290:Ferric Compounds; D017392:Thiobarbituric Acid Reactive Substances; D017638:Asbestos, Crocidolite; D017639:Asbestos, Amosite; D001194:Asbestos; D003855:Deoxyribose