Mechanism of DNA damage by cadmium and interplay of antioxidant enzymes and agents.
Cadmium is an environmental toxicant, which causes cancer in different organs. It was found that it damages DNA in the various tissues and cultured cell lines. To investigate the mechanism of DNA damage, we have studied the effect of cadmium-induced DNA damage in plasmid pBR322 DNA, and the possible ameliorative effects of antioxidative agents under in vitro conditions. It was observed that cadmium alone did not cause DNA damage. However, it caused DNA damage in the presence of hydrogen peroxide, in a dose dependent manner, because of production of hydroxyl radicals. Findings from this study show the conversion of covalently closed circular double-stranded pBR 322 DNA to the open circular and linear forms of DNA when treated with 10 muM cadmium and various concentrations of H(2)O(2). The conversion was due to nicking in DNA strands. The observed rate of DNA strand breakage was dependent on H(2)O(2) concentration, temperature, and time. Metallothionein I failed to prevent cadmium-induced DNA nicking in the presence of H(2)O(2). Of the two antioxidant enzymes (catalase and superoxide dismutase) studied, only catalase conferred significant (50-60%) protection. EDTA and DMSO exhibited protection similar to catalase, while mannitol showed only about 20% protection against DNA damage. Ethyl alcohol failed to ameliorate cadmium-induced DNA strands break. From this study, it is plausible to infer that cadmium in the presence of hydrogen peroxide causes DNA damage probably by the formation of hydroxyl ions. These results may indicate that cadmium in vivo could play a major role in the DNA damage induced by oxidative stress.
Badisa
Veera L D
VL
Department of Biology, Florida A&M University, Tallahassee, Florida 32307, USA.
Latinwo
Lekan M
LM
Odewumi
Caroline O
CO
Ikediobi
Christopher O
CO
Badisa
Ramesh B
RB
Ayuk-Takem
Lambert T
LT
Nwoga
Jude
J
West
John
J
D002104:Cadmium / Q000737:chemistry / Q000633:toxicity*; D002374:Catalase / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D004247:DNA / Q000187:drug effects; D053904:DNA Breaks, Single-Stranded; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000737:chemistry / Q000633:toxicity*; D017665:Hydroxyl Radical / Q000737:chemistry; D008353:Mannitol / Q000494:pharmacology; D008668:Metallothionein / Q000494:pharmacology; D016877:Oxidants / Q000737:chemistry / Q000633:toxicity*; D010957:Plasmids; D013482:Superoxide Dismutase / Q000494:pharmacology; D013696:Temperature
D002614:Chelating Agents; D016166:Free Radical Scavengers; D016877:Oxidants; D002104:Cadmium; D017665:Hydroxyl Radical; D000431:Ethanol; D008353:Mannitol; D004247:DNA; D008668:Metallothionein; D004492:Edetic Acid; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D004121:Dimethyl Sulfoxide