Cadmium-induced 8-hydroxydeoxyguanosine formation, DNA strand breaks and antioxidant enzyme activities in lymphoblastoid cells.
The effect of cadmium ion (Cd) and ascorbic acid (Asc) on the induction of oxidative DNA damage and on the activities of antioxidant enzymes were investigated in human lymphoblastoid cells (AHH-1 TK+/-). Cd at low concentrations of 5-35 microM induced the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and caused nuclear DNA strand breaks. The formation both of 8-OHdG and of DNA strand breaks was dose-dependent at the low Cd concentration; both parameters were linearly correlated with each other (R = 0.932 and P = 0.0209). 8-OHdG formation by Cd plateaued at a Cd concentration of 50 microM. Asc also induced 8-OHdG formation, but it had no synergistic effect with Cd on the formation of 8-OHdG or DNA strand breaks. Cd at the concentration of 50 microM induced the nuclear activity of the antioxidant enzymes, catalase and superoxide dismutase (SOD). Furthermore, Cd caused a decrease in the concentration of reduced glutathione (GSH) and an increase in concentration of the oxidized form (GSSG). While Asc had no observable effect on SOD activity, it did increase nuclear catalase activity in cells. This effect on catalase was synergistic with that of Cd. The linear correlation between 8-OHdG and DNA strand breaks induced by Cd at the lower Cd concentrations (< or = 50 microM), suggested that the extent of formation of DNA strand breaks induced by Cd may be offset by their induction of the formation of 8-OHdG and antioxidant enzyme activities.
Mikhailova
M V
MV
National Center for Toxicological Research, FDA, Jefferson, AR 72079, USA.
Littlefield
N A
NA
Hass
B S
BS
Poirier
L A
LA
Chou
M W
MW
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000975:Antioxidants / Q000378:metabolism* / Q000494:pharmacology; D001205:Ascorbic Acid / Q000633:toxicity; D002104:Cadmium / Q000633:toxicity*; D002374:Catalase / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000187:drug effects* / Q000378:metabolism; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000096:biosynthesis; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism*; D010084:Oxidation-Reduction; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism
D000975:Antioxidants; D002104:Cadmium; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D002374:Catalase; D013482:Superoxide Dismutase; D003849:Deoxyguanosine; D005978:Glutathione; D001205:Ascorbic Acid