[ RadSafe ] FW: [downwinders] DU health effects research 1 Dec

Sat Dec 2 14:37:52 CST 2006

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Subject: [downwinders] DU health effects research 1 Dec

Arch Toxicol. 2006 Nov 24; [Epub ahead of print]
<http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?itool=AbstractPlus-def&P
rId=3055&uid=17124605&db=pubmed&url=http://dx.doi.org/10.1007/s00204-006-016
7-0> Click here to read  Links 

Uranium induces oxidative stress in lung epithelial cells.

*
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pu
bmed_AbstractPlus&term=%22Periyakaruppan+A%22%5BAuthor%5D> Periyakaruppan A,

*
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pu
bmed_AbstractPlus&term=%22Kumar+F%22%5BAuthor%5D> Kumar F, 

*
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pu
bmed_AbstractPlus&term=%22Sarkar+S%22%5BAuthor%5D> Sarkar S, 

*
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pu
bmed_AbstractPlus&term=%22Sharma+CS%22%5BAuthor%5D> Sharma CS, 

*
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pu
bmed_AbstractPlus&term=%22Ramesh+GT%22%5BAuthor%5D> Ramesh GT. 

Molecular Neurotoxicology Laboratory/Proteomics Core, Department of Biology,
Texas Southern University, 3100 Cleburne St, Houston, TX, 77004, USA,
ramesh_gt at tsu.edu.

Uranium compounds are widely used in the nuclear fuel cycle, antitank
weapons, tank armor, and also as a pigment to color ceramics and glass.
Effective management of waste uranium compounds is necessary to prevent
exposure to avoid adverse health effects on the population. Health risks
associated with uranium exposure includes kidney disease and respiratory
disorders. In addition, several published results have shown uranium or
depleted uranium causes DNA damage, mutagenicity, cancer and neurological
defects. In the current study, uranium toxicity was evaluated in rat lung
epithelial cells. The study shows uranium induces significant oxidative
stress in rat lung epithelial cells followed by concomitant decrease in the
antioxidant potential of the cells. Treatment with uranium to rat lung
epithelial cells also decreased cell proliferation after 72 h in culture.
The decrease in cell proliferation was attributed to loss of total
glutathione and superoxide dismutase in the presence of uranium. Thus the
results indicate the ineffectiveness of antioxidant system's response to the
oxidative stress induced by uranium in the cells.

PMID: 17124605 [PubMed - as supplied by publisher]

1: Biochim Biophys Acta. 2006 Oct 19; [Epub ahead of print]
<http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?itool=AbstractPlus-def&P
rId=3048&uid=17118558&db=pubmed&url=http://linkinghub.elsevier.com/retrieve/
pii/S0304-4165(06)00305-9> Click here to read  Links 

In vivo effects of chronic contamination with depleted uranium on vitamin
D(3) metabolism in rat.

*
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pu
bmed_AbstractPlus&term=%22Tissandie+E%22%5BAuthor%5D> Tissandie E, 

*
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pu
bmed_AbstractPlus&term=%22Gueguen+Y%22%5BAuthor%5D> Gueguen Y, 

*
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pu
bmed_AbstractPlus&term=%22Lobaccaro+JM%22%5BAuthor%5D> Lobaccaro JM, 

*
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pu
bmed_AbstractPlus&term=%22Grandcolas+L%22%5BAuthor%5D> Grandcolas L, 

*
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pu
bmed_AbstractPlus&term=%22Voisin+P%22%5BAuthor%5D> Voisin P, 

*
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pu
bmed_AbstractPlus&term=%22Aigueperse+J%22%5BAuthor%5D> Aigueperse J, 

*
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pu
bmed_AbstractPlus&term=%22Gourmelon+P%22%5BAuthor%5D> Gourmelon P, 

*
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pu
bmed_AbstractPlus&term=%22Souidi+M%22%5BAuthor%5D> Souidi M. 

Institute for Radiological Protection and Nuclear Safety, Radiological
Protection and Human health Division, Radiobiology and Epidemiology
Department, Laboratory of Experimental Toxicology, BP no. 17, F-92262
Fontenay-aux-Roses CEDEX, France.

The extensive use of depleted uranium (DU) in today's society results in the
increase of the number of human population exposed to this radionuclide. The
aim of this work was to investigate in vivo the effects of a chronic
exposure to DU on vitamin D(3) metabolism, a hormone essential in mineral
and bone homeostasis. The experiments were carried out in rats after a
chronic contamination for 9 months by DU through drinking water at 40 mg/L
(1 mg/rat/day). This dose corresponds to the double of highest concentration
found naturally in Finland. In DU-exposed rats, the active vitamin D
(1,25(OH)(2)D(3)) plasma level was significantly decreased. In kidney, a
decreased gene expression was observed for cyp24a1, as well as for vdr and
rxralpha, the principal regulators of CYP24A1. Similarly, mRNA levels of
vitamin D target genes ecac1, cabp-d28k and ncx-1, involved in renal calcium
transport were decreased in kidney. In the brain lower levels of messengers
were observed for cyp27a1 as well as for lxrbeta, involved in its
regulation. In conclusion, this study showed for the first time that DU
affects both the vitamin D active form (1,25(OH)(2)D(3)) level and the
vitamin D receptor expression, and consequently could modulate the
expression of cyp24a1 and vitamin D target genes involved in calcium
homeostasis.

PMID: 17118558 [PubMed - as supplied by publisher]

1: Toxicology. 2006 Oct 17; [Epub ahead of print]
<http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?itool=AbstractPlus-def&P
rId=3048&uid=17126469&db=pubmed&url=http://linkinghub.elsevier.com/retrieve/
pii/S0300-483X(06)00606-8> Click here to read  Links 

Effect of acetaminophen administration to rats chronically exposed to
depleted uranium.

*
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pu
bmed_AbstractPlus&term=%22Gueguen+Y%22%5BAuthor%5D> Gueguen Y, 

*
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pu
bmed_AbstractPlus&term=%22Grandcolas+L%22%5BAuthor%5D> Grandcolas L, 

*
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pu
bmed_AbstractPlus&term=%22Baudelin+C%22%5BAuthor%5D> Baudelin C, 

*
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pu
bmed_AbstractPlus&term=%22Grison+S%22%5BAuthor%5D> Grison S, 

*
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pu
bmed_AbstractPlus&term=%22Tissandie+E%22%5BAuthor%5D> Tissandie E, 

*
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pu
bmed_AbstractPlus&term=%22Jourdain+JR%22%5BAuthor%5D> Jourdain JR, 

*
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pu
bmed_AbstractPlus&term=%22Paquet+F%22%5BAuthor%5D> Paquet F, 

*
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pu
bmed_AbstractPlus&term=%22Voisin+P%22%5BAuthor%5D> Voisin P, 

*
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pu
bmed_AbstractPlus&term=%22Aigueperse+J%22%5BAuthor%5D> Aigueperse J, 

*
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pu
bmed_AbstractPlus&term=%22Gourmelon+P%22%5BAuthor%5D> Gourmelon P, 

*
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pu
bmed_AbstractPlus&term=%22Souidi+M%22%5BAuthor%5D> Souidi M. 

Institute for Radiological Protection and Nuclear Safety, Radiological
Protection and Human Health Division, Radiobiology and Epidemiology
Department, Laboratory of Experimental Toxicology, BP No. 17, F-92262
Fontenay-aux-Roses Cedex, France.

The extensive use of depleted uranium (DU) in both civilian and military
applications results in the increase of the number of human beings exposed
to this compound. We previously found that DU chronic exposure induces the
expression of CYP enzymes involved in the metabolism of xenobiotics (drugs).
In order to evaluate the consequences of these changes on the metabolism of
a drug, rats chronically exposed to DU (40mg/l) were treated by
acetaminophen (APAP, 400mg/kg) at the end of the 9-month contamination.
Acetaminophen is considered as a safe drug within the therapeutic range but
in the case of overdose or in sensitive animals, hepatotoxicity and
nephrotoxicity could occur. In the present work, plasma concentration of
APAP was higher in the DU group compared to the non-contaminated group. In
addition, administration of APAP to the DU-exposed rats increased plasma ALT
(p<0.01) and AST (p<0.05) more rapidly than in the control group.
Nevertheless, no histological alteration of the liver was observed but renal
injury characterized by incomplete proximal tubular cell necrosis was higher
for the DU-exposed rats. Moreover, in the kidney, CYP2E1 gene expression, an
important CYP responsible for APAP bioactivation and toxicity, is increased
(p<0.01) in the DU-exposed group compared to the control group. In the
liver, CYP's activities were decreased between control and DU-exposed rats.
These results could explain the worse elimination of APAP in the plasma and
confirm our hypothesis of a modification of the drug metabolism following a
DU chronic contamination.

PMID: 17126469 [PubMed - as supplied by publisher]

1: J Toxicol Environ Health A. 2006 Sep;69(17):1613-28.
<http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?itool=AbstractPlus-def&P
rId=3396&uid=16854789&db=pubmed&url=http://taylorandfrancis.metapress.com/In
dex/10.1080/15287390600629825> Click here to read  Links 

Short-term effects of depleted uranium on immune status in rat intestine.

*
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pu
bmed_AbstractPlus&term=%22Dublineau+I%22%5BAuthor%5D> Dublineau I, 

*
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pu
bmed_AbstractPlus&term=%22Grison+S%22%5BAuthor%5D> Grison S, 

*
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pu
bmed_AbstractPlus&term=%22Linard+C%22%5BAuthor%5D> Linard C, 

*
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pu
bmed_AbstractPlus&term=%22Baudelin+C%22%5BAuthor%5D> Baudelin C, 

*
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pu
bmed_AbstractPlus&term=%22Dudoignon+N%22%5BAuthor%5D> Dudoignon N, 

*
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pu
bmed_AbstractPlus&term=%22Souidi+M%22%5BAuthor%5D> Souidi M, 

*
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pu
bmed_AbstractPlus&term=%22Marquette+C%22%5BAuthor%5D> Marquette C, 

*
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pu
bmed_AbstractPlus&term=%22Paquet+F%22%5BAuthor%5D> Paquet F, 

*
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pu
bmed_AbstractPlus&term=%22Aigueperse+J%22%5BAuthor%5D> Aigueperse J, 

*
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pu
bmed_AbstractPlus&term=%22Gourmelon+P%22%5BAuthor%5D> Gourmelon P. 

Institut de Radioprotection et de Surete Nucleaire, Direction de la
RadioProtection de l'Homme, Service de Radiobiologie et d'Epidemiologie,
Laboratoire de Radiotoxicologie Experimentale IRSN, Fontenay-aux-Roses
Cedex, France. isabelle.dublineau at irsn.fr

In the event of ingestion, the digestive tract is the first biological
system exposed to depleted uranium (DU) intake via the intestinal lumen.
However, little research has addressed the biological consequences of a
contamination with depleted uranium on intestinal properties such as the
barrier function and/or the immune status of this tissue. The aim of this
study was to determine if the ingestion of depleted uranium led to changes
in the gut immune system of the intestine. The experiments were performed at
1 and 3 d following a per os administration of DU to rats at sublethal dose
(204 mg/kg). Several parameters referring to the immune status, such as gene
and protein expressions of cytokines and chemokines, and localization and
density of immune cell populations, were assessed in the intestine. In
addition, the overall toxicity of DU on the small intestine was estimated in
this study, with histological appearance, proliferation rate,
differentiation pattern, and apoptosis process. Firstly, the results of this
study indicated that DU was not toxic for the intestine, as measured by the
proliferation, differentiation, and apoptosis processes. Concerning the
immune properties of the intestine, the ingestion of depleted uranium
induced some changes in the production of chemokines and in the expression
of cytokines. A diminished production of monocyte chemoattractant protein-1
(MCP-1) was noted at 1 day post exposure. At 3 d, the increased gene
expression of interferon gamma (IFNgamma) was associated with an enhanced
mRNA level of Fas ligand, suggesting an activation of the apoptosis pathway.
However, no increased apoptotic cells were observed at 3 d in the
contaminated animals. There were no changes in the localization and density
of neutrophils, helper T lymphocytes, and cytotoxic T lymphocytes after DU
administration. In conclusion, these results suggest that depleted uranium
is not toxic for the intestine after acute exposure. Nevertheless, DU seems
to modulate the expression and/or production of cytokines (IFNgamma) and
chemokines (MCP-1) in the intestine. Further experiments need to be
performed to determine if a chronic contamination at low dose leads in the
long term to modifications of cytokines/chemokines patterns, and to
subsequent changes in immune response of the intestine.

PMID: 16854789 [PubMed - indexed for MEDLINE]

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