ASBESTOS-INDUCED OXIDATIVE INJURY TO DNA

DNA-damaging effects of asbestos in the presence of organic peroxides and hydroperoxides were investigated. The destabilization of the secon dary structure of DNA, damage to deoxyribose sugar and DNA fidelity we re measured, respectively, by S-1 nuclease hydrolysis, the formation o f thiobarbituric acid (TBA)-reacting species and a melting temperature (T(m)) profile using calf thymus DNA. S-1 nuclease hydrolysis and T(m ) determinations have shown that the presence of benzoylperoxide (BOOB ), cumene hydroperoxide (COOH) or tertiary-butyl hydroperoxide (t-BOOH ) increased asbestos-mediated DNA damage by a large factor compared ei ther to asbestos alone or to peroxide or hydroperoxide alone. However, no formation of TBA-reacting species could be observed in this system . The quenchers of reactive oxygen species (ROS) afforded protection a gainst DNA damage. These results suggest that asbestos in the presence of organic peroxides and hydroperoxides damage the DNA which is media ted by the generation of oxygen free radicals. The significance of the se results in relation to the development of cancer of the respiratory tract among the asbestos exposed population is discussed.