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ARSENIC SPECIES THAT CAUSE RELEASE OF IRON FROM FERRITIN AND GENERATION OF ACTIVATED OXYGEN
Citation:
Ahmad, S, K T. Kitchin, AND W. R. Cullen. ARSENIC SPECIES THAT CAUSE RELEASE OF IRON FROM FERRITIN AND GENERATION OF ACTIVATED OXYGEN. Presented at 2000 NIEHS/NTA Biomedical Science Fair, NIEHS, RTP, NC, April 28, 2000.
Description:
ABSTRACT
The in vitro effects of four different species of arsenic { arsenate, arsenite, monomethylarsonic acid and dimethylarsinic acid) in mobilizing iron from horse spleen ferritin under aerobic and anaerobic conditions were investigated. Dimethylarsinicacid {DMA(V)), and dimethylarsinousacid {DMA(III), significantly released iron from horse spleen ferritin either with or without the presence of ascorbic acid, a strong synergistic agent. Ascorbic acid-mediated iron release was time dependent as well as both DMA(III) and ferritin concentration dependent. Iron release from ferritin by DMA(III) alone or with ascorbic acid was not significantly inhibited by superoxide dismutase {150 or 300 units/mi). However, the iron release was greater under anaerobic conditions {nitrogen gas) which indicates direct chemical reduction of iron from ferritin by DMA('I') with or without ascorbic acid. Both DMA(V) and DMA(III) released iron from both horse spleen and human liver ferritin. Further, the release of ferritin-iron by DMA(III) with ascorbic acid catalyzed bleomycin-dependent degradation of calf thymus DNA. These results indicate that exogenous methylated arsenic species and endogenous ascorbic acid can cause {a) the release of iron from ferritin and {b) the iron-dependent formation of reactive oxygen species and {c) DNA damage. This reactive oxygen species pathway could be a mechanism of action of arsenic carcinogenesis in man.
This is an abstract of a proposed presentation and does not necessarily reflect EPA policy.