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 mesothelioma. Although chromosomal changes have been documented in mesothelial cells, the mechanisms of interaction of crocidolite with DNA remain obscure. Since human mesothelial cells are exquisitely sensitive to asbestos, oxidative DNA damage was measured in an asbestos-exposed human mesothelial cell line (MET5A) by assaying oxidized guanine bases [8-oxo-2'-deoxyguanosine (oxo8dG), 8-oxoguanine (oxo8G), and 8-oxoguanosine (oxo8Gua)] 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, nonfibrous analog of crocidolite did not cause increased adduct release. Results show that oxidative RNA and DNA bases are produced in response to asbestos in target cells of asbestos-induced cancers.
Chen
Q
Q
Department of Biochemistry and Molecular Biology, University of California, Berkeley 94720, USA.
Marsh
J
J
Ames
B
B
Mossman
B
B
D000080242:8-Hydroxy-2'-Deoxyguanosine; D017638:Asbestos, Crocidolite / Q000633:toxicity*; D015415:Biomarkers / Q000032:analysis; D002273:Carcinogens / Q000633:toxicity*; D002460:Cell Line; D003470:Culture Media; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis; D004848:Epithelium / Q000737:chemistry / Q000187:drug effects; D006147:Guanine / Q000031:analogs & derivatives / Q000032:analysis; D006151:Guanosine / Q000031:analogs & derivatives / Q000032:analysis; D006801:Humans; D010084:Oxidation-Reduction; D010994:Pleura / Q000737:chemistry* / Q000187:drug effects*
D015415:Biomarkers; D002273:Carcinogens; D003470:Culture Media; D017638:Asbestos, Crocidolite; D006151:Guanosine; C046215:8-hydroxyguanosine; C024829:8-hydroxyguanine; D006147:Guanine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine