ARSENIC-INDUCED DNA-STRAND BREAKS ASSOCIATED WITH DNA-PROTEIN CROSS-LINKS 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 muM produced DNA-protein crosslinks, while at 10 muM 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 muM 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.