Arsenic-induced DNA-strand breaks associated with DNA-protein crosslinks in human fetal lung fibroblasts.
Sodium arsenite (As)-induced DNA damage was measured in human fetal lung fibroblasts (2BS cells) by an alkaline elution technique and a fluorometric DNA assay. Sodium arsenite at 1-5 microM produced DNA-protein crosslinks, while at 10 microM this effect was not observed. Deproteinization of DNA-protein complexes revealed protein-associated DNA-strand breaks. Both DNA-protein crosslinks and DNA-strand breaks were concentration-dependent; 3 microM As was the most efficient dose. Arsenic mediated DNA-protein interactions may play a major role in arsenic carcinogenesis, and the induced protein-associated DNA-strand breaks could provide an explanation for chromosome aberrations and sister-chromatid exchanges induced by arsenic in vivo and in vitro.
Dong
J T
JT
Cancer Institute, Chinese Academy of Medical Sciences, Beijing.
Luo
X M
XM
D001151:Arsenic / Q000633:toxicity*; D018053:Arsenites; D002478:Cells, Cultured; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D019286:Endopeptidase K; D005347:Fibroblasts / Q000187:drug effects / Q000648:ultrastructure; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000196:embryology; D008769:Methylnitronitrosoguanidine; D011506:Proteins / Q000737:chemistry*; D012697:Serine Endopeptidases; D017670:Sodium Compounds; D013439:Sulfhydryl Reagents / Q000633:toxicity*
D018053:Arsenites; D011506:Proteins; D017670:Sodium Compounds; D013439:Sulfhydryl Reagents; D008769:Methylnitronitrosoguanidine; C017947:sodium arsenite; D004247:DNA; D012697:Serine Endopeptidases; D019286:Endopeptidase K; D001151:Arsenic