Plasmid DNA damage caused by methylated arsenicals, ascorbic acid and human liver ferritin.
Both dimethylarsinic acid (DMA(V)) and dimethylarsinous acid (DMA(III)) release iron from human liver ferritin (HLF) with or without the presence of ascorbic acid. With ascorbic acid the rate of iron release from HLF by DMA(V) was intermediate (3.37 nM/min, P<0.05) and by DMA(III) was much higher (16.3 nM/min, P<0.001). No pBR322 plasmid DNA damage was observed from in vitro exposure to arsenate (iAs(V)), arsenite (iAs(III)), monomethylarsonic acid (MMA(V)), monomethylarsonous acid (MMA(III)) or DMA(V) alone. DNA damage was observed following DMA(III) exposure; coexposure to DMA(III) and HLF caused more DNA damage; considerably higher amounts of DNA damage was caused by coexposure of DMA(III), HLF and ascorbic acid. Diethylenetriaminepentaacetic acid (an iron chelator), significantly inhibited DNA damage. Addition of catalase (which can increase Fe(2+) concentrations) further increased the plasmid DNA damage. Iron-dependent DNA damage could be a mechanism of action of human arsenic carcinogenesis.
Ahmad
Sarfaraz
S
Mercer University School of Medicine, Division of Basic Medical Sciences, 1550 College Street,, Macon, GA 31207, USA.
Kitchin
Kirk T
KT
Cullen
William R
WR
D001205:Ascorbic Acid / Q000633:toxicity*; D002101:Cacodylic Acid / Q000633:toxicity*; D004249:DNA Damage / Q000187:drug effects*; D004278:DNA, Superhelical / Q000187:drug effects*; D004357:Drug Synergism; D005293:Ferritins / Q000187:drug effects / Q000378:metabolism*; D006540:Herbicides / Q000633:toxicity*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000627:therapeutic use; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D004369:Pentetic Acid / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000378:metabolism
D004278:DNA, Superhelical; D006540:Herbicides; D007502:Iron Chelating Agents; D017382:Reactive Oxygen Species; D004369:Pentetic Acid; D005293:Ferritins; D002101:Cacodylic Acid; D007501:Iron; D001205:Ascorbic Acid