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ARSENIC SPECIES CAUSE RELEASE OF IRON FROM FERRITIN GENERATING REACTIVIE OXYGEN SPECIES
Citation:
Ahmad, S, K T. Kitchin, AND W. R. Cullen. ARSENIC SPECIES CAUSE RELEASE OF IRON FROM FERRITIN GENERATING REACTIVIE OXYGEN SPECIES. Presented at 1st Int'l Symposium on HO/CO, New York City, NY, 7/14-17/2000.
Description:
ARSENIC SPECIES. CAUSE RELEASE OF IRON , FROM FERRITIN GENERATING REACTIVE OXYGEN SPECIES
Arsenic-associated cancer (lung, bladder, skin, liver, kidney) remains a significant world- wide public health problem (e.g., Taiwan, Chile, Bangladesh, India, China and Thailand). Recent studies inrjicate that arsenic may generate reactive oxygen species (ROS) (e. g. dimethylarsenic peroxyl radical, superoxide anion or hydroxyl radicals) causing cellular toxicity and/or carcinogenicity. The action(s) of arsenic at the cellular level and possible arsenic interaction(s) with iron (Fe) are not well understood.
The present in vitro studies investigated the potential role of different arsenic species, arsenate, arsenite, monomethylarsonic acid and dimethylarsinic acid (DMA), to release Fe from ferritin. DMA, particularly in the +3 oxidation state, significantly released Fe from horse spleen ferritin either with or without the presence of ascorbic acid, a strong synergistic agent. The presence of oxyradical scavengers, mannitol, benzoic acid or superoxide dismutase, inhibited the DMA(III) and ascorbic acid-mediated Fe release from ferritin by 38%, 51% and 15%, respectively. Since the redox cycling of free Fe is closely associated with the production of ROS, we studied the pro-oxidant activity of Fe released from ferritin by DMA(III) and ascorbic acid. Iron release.d from ferritin by DMA(III) and ascorbic acid catalyzed bleomycin-dependent
calf thymus DNA degradation.
In summary, methylated arsenic chemical forms and endogenous ascorbic acid cause the release of Fe from ferritin and the Fe-dependent formation of ROS; these ROS could be a mechanism of action of arsenic carcinogenesis in man.
This is an abstract ofa proposed presentation and does not necessarily reflect EPA policy.