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Accumulation and toxicity of monophenyl arsenicals in rat endothelial cells
Hirano, S., Kobayashi, Y., Hayakawa, T., Cui, X., Yamamoto, M., Kanno, S. and Shraim, A. (2005) Accumulation and toxicity of monophenyl arsenicals in rat endothelial cells. Archives Of Toxicology, 79 1: 54-61.
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| Author(s) |
Hirano, S.
Kobayashi, Y.
Hayakawa, T.
Cui, X.
Yamamoto, M.
Kanno, S.
Shraim, A.
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| Title |
Accumulation and toxicity of monophenyl arsenicals in rat endothelial cells
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| Journal name |
Archives Of Toxicology
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| Publication date |
2005
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| Volume number |
79
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| Issue number |
1
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| ISSN |
0340-5761
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| Start page |
54
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| End page |
61
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| Total pages |
8
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| Editor(s) |
H. Bolt
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| Place of publication |
New York
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| Publisher |
Springer
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| Collection year |
2005
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| Language |
eng
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| Subject |
C1
321299 Public Health and Health Services not elsewhere classified
730210 Environmental health
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| Abstract |
Clark 1 (diphenylarsine chloride) and Clark 2 ( diphenylarsine cyanide) were used as chemical weapon agents (CWA), and the soil contamination by these CWA and their degraded products, diphenyl and phenyl arsenicals, has been one of the most serious environmental issues. In a series of comparisons in toxicity between trivalent and pentavalent arsenicals we investigated differences in the accumulation and toxicity of phenylarsine oxide (PAO(3+)) and phenylarsonic acid (PAA(5+)) in rat heart microvascular endothelial cells. Both the cellular association and toxicity of PAO(3+) were much higher than those of PAA(5+), and LC50 values of PAO(3+) and PAA(5+) were calculated to be 0.295 muM and 1.93 mM, respectively. Buthionine sulfoximine, a glutathione depleter, enhanced the cytotoxicity of both PAO(3+) and PAA(5+). N-Acetyl-L-cysteine (NAC) reduced the cytotoxicity and induction of heme oxygenase-1 (HO-1) mRNA in PAO(3+)-exposed cells, while NAC affected neither the cytotoxicity nor the HO-1 mRNA level in PAA(5+)-exposed cells. The effect of NAC may be due to a strong affinity of PAO(3+) to thiol groups because both NAC and GSH inhibited the cellular accumulation of PAO(3+), but PAA(3+) increased tyrosine phosphorylation levels of cellular proteins. These results indicate that the inhibition of protein phosphatases as well as the high affinity to cellular components may confer PAO(3+) the high toxicity.
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| Keyword(s) |
phenylarsine oxide
phenylarsonic acid
cytotoxicity
endothelial cell
heme oxygenase-1
N-acetyl-L-cysteine
glutathione
buthionine sulfoximine
inductively coupled plasma mass spectrometry
Lung Epithelial-cells
Warfare Agents
Organoarsenic Compounds
Methylated Arsenicals
Dimethylarsinic Acid
In-vitro
Trivalent
Exposure
Difference
Mice
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