Effect of iron acquisition on induction of DNA single-strand breaks by erionite, a carcinogenic mineral fiber.
It has been proposed that iron from inhaled fibers, such as asbestos, is responsible for their toxicity and carcinogenicity. The natural fibrous zeolite erionite is far more carcinogenic than asbestos, but contains little or no iron. Fibers that persist in the lung accumulate iron on their surfaces. The ability of erionite to induce formation of single-strand breaks in phi X174 RFI DNA was investigated before and after binding of iron. Unmodified erionite did not induce DNA single-strand breaks with or without ascorbate and/or the iron chelator EDTA. When erionite (1 mg/ml) was suspended in 25, 50, 100, or 500 microM FeCl2, it readily bound iron (25, 50, 93, or 176 nmol Fe/mg, respectively, in 1 h), apparently through ion exchange. When erionite was suspended in FeCl3 at identical concentrations for 1 h, it also bound iron (24, 46, 89, or 239 nmol Fe/mg). The ferric iron did not appear to bind primarily through ion exchange, but appeared to be deposited on the surface, probably in the form of hydroxides/oxyhydroxides. When ferrous iron was bound to erionite, single-strand breaks in DNA were induced in the absence of ascorbate, but when ferric iron was bound, DNA single-strand breaks were observed only in the presence of ascorbate. When EDTA or citrate was added, this activity increased with the amount of iron mobilized from the fiber. If iron acquired by erionite in vivo is similarly mobilized, it may damage biomolecules throughout the cell, including DNA. This may explain the toxicity and carcinogenicity of erionite.
Eborn
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Department of Chemistry and Biochemistry, Utah State University, Logan 84322-0300.
Aust
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D002273:Carcinogens / Q000494:pharmacology* / Q000633:toxicity; D002412:Cations / Q000032:analysis; D004249:DNA Damage; D004279:DNA, Viral / Q000187:drug effects; D003676:Deferoxamine / Q000494:pharmacology; D005290:Ferric Compounds / Q000494:pharmacology; D005296:Ferrous Compounds / Q000494:pharmacology; D007501:Iron / Q000494:pharmacology*; D017641:Zeolites / Q000494:pharmacology* / Q000633:toxicity
D002273:Carcinogens; D002412:Cations; D004279:DNA, Viral; D005290:Ferric Compounds; D005296:Ferrous Compounds; C083174:erionite; D017641:Zeolites; D007501:Iron; D003676:Deferoxamine