DETECTION OF 8-OXO-2'-DEOXYGUANOSINE, A MARKER OF OXIDATIVE DNA-DAMAGE, IN CULTURE-MEDIUM FROM HUMAN MESOTHELIAL CELLS EXPOSED TO CROCIDOLITE ASBESTOS

Crocidolite asbestos is associated with the development of mesotheliom a. Although chromosomal changes have been documented in mesothelial ce lls, the mechanisms of interaction of crocidolite with DNA remain obsc ure, Since human mesothelial cells are exquisitely sensitive to asbest os, oxidative DNA damage was measured in an asbestos-exposed human mes othelial cell line (MET5A) by assaying oxidized guanine bases [8-oxo-2 '-deoxyguanosine (oxo(8)dG), 8-oxoguanine (oxo(8)G), and 8-oxoguanosin e (oxo(8)Gua)] excreted into the spent culture medium after DNA repair or turnover, At growth inhibitory, but not cytolytic concentrations, asbestos caused significant elevation of all bases in the spent medium over a 48-h period, In contrast, riebeckite, a chemically similar, no nfibrous analog of crocidolite did not cause increased adduct release, Results show that oxidative RNA and DNA bases are produced in respons e to asbestos in target cells of asbestos-induced cancers.