TY - JOUR
T1 - Detection of 8-oxo-2'-deoxyguanosine, a marker of oxidative DNA damage, in culture medium from human mesothelial cells exposed to crocidolite asbestos
AU - Chen, Qin
AU - Marsh, Joanne
AU - Ames, Bruce
AU - Mossman, Brooke
N1 - Funding Information:
We thank B.Ravenellc, J.Kessler and T.Quinn for technical assistance with the preparation of the manuscript and figures. We are grateful to Dr P.Vacek, Department of Biostatistics at UVM, who provided statistical analyses of data. Research was supported by grants ES06667 (BTM), ES06499 (BTM) and ES01896 (BNA) from NIEHS, and CA39910 from NCI (BNA). Q.Chen is a recipient of the Colgate-Palmolive postdoctoral award from the Society of Toxicology.
PY - 1996/11
Y1 - 1996/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0029803172&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029803172&partnerID=8YFLogxK
U2 - 10.1093/carcin/17.11.2525
DO - 10.1093/carcin/17.11.2525
M3 - Article
C2 - 8968073
AN - SCOPUS:0029803172
SN - 0143-3334
VL - 17
SP - 2525
EP - 2527
JO - Carcinogenesis
JF - Carcinogenesis
IS - 11
ER -