Alterations in gene expression in cultured human cells after acute exposure to uranium salt: Involvement of a mineralization regulator.
The risk of exposure of workers or populations to materials, such as uranium, of nuclear fuel process origins is a major concern worldwide. Our goal is to improve the knowledge of mechanisms ruling its chemical toxicity, and to search for proteins as potential indicator of effect. Such a marker of internal damage remains to be discovered in the case of uranium. This study, based on DNA microarrays, reports a comparative gene expression analysis following acute uranium exposure of several human cell lines taken from kidneys or lungs as representative targets. Among uranium altered genes, no common gene was found between cells originating from lungs and kidney. In contrast, a set of 24 altered genes was common to two kidney cell lines. Transcriptional levels of a subset of renal genes were assessed with qRT-PCR. Furthermore, we highlighted a gene (SPP1) coding for a secreted protein (osteopontin) linked to ectopic mineralization. Immunoblotting assays showed that uranyl ions affect the excretion of osteopontin in a time- and dose-dependent manner. We consider that osteopontin, described as associated with bone resorbtion and kidney mineral stones, is a worthwhile candidate to be tested in vivo as a potential indicator of uranyl mineralization effects.
Prat
Odette
O
CEA, IBEB, SBTN, Bagnols-sur-Cèze, France. odette.prat@cea.fr
Bérenguer
Frédéric
F
Steinmetz
Gérard
G
Ruat
Sylvie
S
Sage
Nicole
N
Quéméneur
Eric
E
D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D018613:Microscopy, Confocal; D008903:Minerals / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D053495:Osteopontin / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000096:biosynthesis / Q000235:genetics; D011507:Proteinuria / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013056:Spectrophotometry, Ultraviolet; D017974:Uranium Compounds / Q000378:metabolism / Q000633:toxicity*
D008565:Membrane Proteins; D008903:Minerals; D017974:Uranium Compounds; D053495:Osteopontin; D012313:RNA; C401298:sphingosine-1-phosphate phosphatase; D010744:Phosphoric Monoester Hydrolases