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Plasmid DNA damage caused by methylated arsenicals, ascorbic acid and human liver ferritin

TitlePlasmid DNA damage caused by methylated arsenicals, ascorbic acid and human liver ferritin
Publication TypeJournal Article
Year of Publication2002
AuthorsAhmad, S, Kitchin, KT, Cullen, WR
JournalToxicology Letters
Volume133
Pagination47-57
Date PublishedJul
Type of ArticleProceedings Paper
ISBN Number0378-4274
Keywordsarsenic, BIOCHEMICAL PARAMETERS, CARCINOGENESIS, DIMETHYLARSINIC ACID, dimethylarsinous acid, DMA(111), DNA damage, ENDOTHELIAL-CELLS, human liver ferritin, INDUCTION, INORGANIC ARSENICS, iron, MICE, MONOMETHYLARSONOUS ACID, reactive oxygen, species, STRAND BREAKS
Abstract

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 Fe2+ concentrations) further increased the plasmid DNA damage. Iron-dependent DNA damage could be a mechanism of action of human arsenic carcinogenesis. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

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