Effect of arsenite on the DNA repair of UV-irradiated Chinese hamster ovary cells.
Arsenite, an ubiquitous human carcinogen, has been shown to enhance the cytotoxicity, mutagenicity and clastogenicity of UV light in mammalian cells. Arsenite may exert its co-genotoxic effects by inhibiting DNA repair. Results from alkaline sucrose gradient sedimentation show that arsenite did not accumulate UV-induced DNA strand breaks in Chinese hamster ovary (CHO) K1 cells as aphidicolin plus hydroxyurea (HU) did. These data indicate that arsenite did not inhibit the activity of DNA polymerase alpha in UV repair. Treatment with arsenite before UV irradiation slightly reduced the DNA strand breaks accumulated by cytosine beta-D-arabinofuranoside (AraC) plus HU. This effect implies that arsenite only slightly inhibited the incision of UV-induced DNA adducts. The low molecular weight DNA accumulated by post-UV incubation with AraC plus HU shifted to high molecular weight upon the incubation of cells in drug-free medium, but this shifting was prohibited by the presence of arsenite. This suggests that arsenite inhibited the rejoining of DNA strand breaks. When a pulse-chase labelling procedure was applied on UV-irradiated cells, the chain elongation of nascent DNA was strongly inhibited by post-incubation with arsenite. These data show that arsenite inhibited post-replication repair in UV-irradiated cells. Therefore, the steps inhibited by arsenite in UV-induced DNA repair in CHO K1 cells are different from human fibroblasts in which the inhibition of excision of pyrimidine dimers by arsenite was reported to be the major target.
Lee-Chen
S F
SF
Institute of Zoology, Academia Sinica, Taipei, Taiwan, ROC.
Yu
C T
CT
Jan
K Y
KY
D000818:Animals; D001151:Arsenic / Q000633:toxicity*; D018053:Arsenites; D016466:CHO Cells; D006224:Cricetinae; D004260:DNA Repair / Q000187:drug effects* / Q000528:radiation effects; D004277:DNA, Single-Stranded / Q000528:radiation effects; D014466:Ultraviolet Rays
D018053:Arsenites; D004277:DNA, Single-Stranded; C015001:arsenite; D001151:Arsenic