Mineral fibers, cigarette smoke, and oxidative DNA damage : An experimental study

• This study concerns the ability of mineral fibers and cigarette smoke to generate reactive oxygen metabolites and to cause damage to DNA. The generation of hydroxyl radicals (OH") was demonstrated by using the DNA base, deoxyguanosine (dG) as a trapping agent for OH" and determining its hydroxylation to 8-hydroxydeoxyguanosine (80HdG), and oxidative DNA damage was assessed as formation of 80HdG in isolated DNA or in DNA of human lung cells in culture. Both asbestos (chrysotile) and manmade mineral fibers (~)were found to generate OH" and damage DNA in aqueous buffer solutions, andmore OH· was generated by the iron-containing rock and slag wools than by glass wool and ceramic fibers. The OH• generation by rock wool was decreased by treatment with heat, oxygen or desferrioxamine, indicating that chemical characteristics including iron on the fiber surface were important determinants of the OH" formation. A variety of natural mineral fibers (asbestos, erionite, and wollastonite) and MMMF (rock wool, glass wool, and ceramic fibers) were found to stimulate polymorphonuclear leukocytes (PMNL) togenerate OH" in the presence of exogenously added iron, and amosite, crocidolite, antophyllite, erionite, and wollastonite caused OH" formation also in the absence of exogenously added iron. Cigarette smoke potentiated the damaging action of rock wool onisolated DNA, suggesting that iron-containing fibers might catalyze O:H" formation from hydrogen peroxide generated in the smoke. Cigarette smoke-induced damage to isolated DNA was inhibited by tyrosinase and catalase, indicating that polyphenols in the smoke,e.g. hydroquinone and catechol, were important for the hydrogen peroxide generation. Cigarette smoke was also found to cause oxidative DNA damage and DNA strand break formation in cultured human lung cells by mechanisms involving OH" attack on the DNAmolecule and endonuclease activation. Moreover, cigarette tar was demonstrated to promote P:MNL-mediated DNA strand-break formation in human lung cells, and tar loaded with iron was more damaging than regular tar.These fmdings indicate that mineral fibers, by producing OH· themselves and by stimulating PMNL to generate OH· in the presence of iron, may cause oxidative DNA damage under experimental conditions. They also indicate that cigarette smoke may cause DNA base hydroxylation and DNA strand-break formation in human lung cells via mechanisms involving OH", and that iron is important for the OH•-formation. Altogether, the findings point to the possibility that mineral fibers may promote OH" generation by cigarette smoke and inflammatory cells and so increase the risk of DNA damage in human lung cells.

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