DIFFERENTIAL ROLE OF HYDROGEN-PEROXIDE AND ORGANIC PEROXIDES AUGMENTING ASBESTOS-MEDIATED DNA-DAMAGE - IMPLICATIONS FOR ASBESTOS-INDUCED CARCINOGENESIS

The incubation of asbestos with DNA in presence of peroxides augmented DNA damage several fold as compared to the damage caused by individua l treatments. Asbestos in presence of hydrogen peroxide causes DNA dou ble strand breaks, damage to its deoxyribose sugar moiety and enhanced DNA fidelity. However, only DNA double strand breaks and enhanced DNA fidelity could be recorded in presence of organic hydroperoxide/perox ide but no DNA sugar damage could be observed. Further, the extent of DNA damage could be correlated to the carcinogenic potential of asbest os fibre. Crocidolite, the most carcinogenic variety of asbestos, prod uces maximum damage to DNA in presence of both hydrogen peroxide and o rganic hydroperoxide/peroxide while chrysolite which is only a co-carc inogen produces significantly less DNA damage. The observed difference s in DNA damage by hydrogen peroxide and organic hydroperoxide/peroxid e have been ascribed to the differential reactivity of DNA with hydrox yl and alkoxy/aryloxy free radicals produced respectively from these i norganic and organic peroxides. (C) 1994 Academic Press, Inc.