Renal toxicogenomic response to chronic uranyl nitrate insult in mice

Magali Taulan (1, 2) , F. Paquet (2) , C. Maubert (2) , O. Delissen (2) , J. Demaille (1) , M.-C. Romey (1)

1 IGH - Institut de génétique humaine
2 IRSN/PSE-SANTE/SESANE/LRTOX - Laboratoire de radiotoxicologie et radiobiologie expérimentale

Although the nephrotoxkity of uranium has been established through numerous animal studies, relatively little is known about the effects of long-term environmental uranium exposure. Using a combination of conventional biochemical studies and serial analysis of gene expression (SAGE), we examined the renal responses to uranyl nitrate (UN) chronic exposure. Renal uranium levels were significantly increased 4 months after ingestion of uranium in drinking water. Creatinine levels in serum were slightly but significantly increased compared with those in controls. Although no further significant differences in other parameters were noted, substantial molecular changes were observed in toxicogenomic profiles. UN induced dramatic alterations in expression levels of more than 200 genes, mainly up-regulated, including oxidative-response-related genes, genes encoding for cellular metabolism, ribosomal proteins, signal transduction, and solute transporters. Seven differentially expressed transcripts were confirmed by real-time quantitative polymerase chain reaction. In addition, significantly increased peroxide levels support the implication of oxidative stress in UN toxicant response. This report highlights the potential of SAGE for the discovery of novel toxicant-induced gene expression alterations. Here, we present, for the first time, a comprehensive view of renal molecular events after uranium long-term exposure.

Mots clés: creatinine; drinking water; ribosome protein; uranyl nitrate; hydrogen peroxide; primer DNA; RNA; animal experiment; article; cell metabolism; controlled study; creatinine blood level; gene expression; long term exposure; mouse; nonhuman; oxidative stress; priority journal; real time polymerase chain reaction; serial analysis of gene expression; signal transduction; toxicogenetics; animal; C57BL mouse; DNA microarray; drug effect; gene expression profiling; gene expression regulation; kidney; metabolism; oral drug administration; randomization; reverse transcription polymerase chain reaction; sequence tagged site; Animalia; Administration; Oral; Animals; DNA Primers; Gene Expression Profiling; Gene Expression Regulation; Hydrogen Peroxide; Kidney; Mice; Inbred C57BL; Oligonucleotide Array Sequence Analysis; Oxidative Stress; Random Allocation; Reverse Transcriptase Polymerase Chain Reaction; Sequence Tagged Sites; Uranyl Nitrate

Domaines: Alimentation et Nutrition; Santé; Santé publique et épidémiologie

Magali Taulan, F. Paquet, C. Maubert, O. Delissen, J. Demaille, et al.. Renal toxicogenomic response to chronic uranyl nitrate insult in mice. Environmental Health Perspectives, 2004, 112 (16), pp.1628-1635. ⟨10.1289/txg.7296⟩. ⟨hal-03048060⟩