From cell to man: Evaluation of osteopontin as a possible biomarker of uranium exposure

BackgroundOre workers are conventionally monitored for exposure by measuring the uranium in their urine, but specific biomarkers of kidney damage still remain to be discovered. A recent toxicogenomics study allowed us to focus on osteopontin (OSTP) normally excreted in human urine and linked to mineral metabolism.ObjectivesWe examined the association between osteopontin and uranium exposure both in vitro, in a human kidney cell model, and in the urine of exposed individuals.MethodsOSTP was measured in supernatants of uranium-exposed HK2 cells to establish a dose–response curve and a time course experiment. Its role was studied through a gene extinction experiment. Uranium and OSTP were then monitored in the urine of exposed nuclear fuel industry workers and a chronically exposed population. These levels were compared with those found in a non-exposed population.ResultsThe study of HK2 cells indicated that OSTP secretion decreased after uranium exposure in a concentration and time dependent manner, but its suppression does not affect cell sensitivity to uranium. In spite of wide inter-individual variability, this parameter decreases also in human urine when urinary uranium exceeds 30 μg/L after an acute exposure, a value considered to be critical for kidney damage.ConclusionThis study reports how toxicogenomics can highlight putative toxicity biomarkers in an easy to access biological fluid. The decrease of urinary osteopontin in response to uranium exposure suggests kidney damage and would thus be complementary to current markers.

Research Highlights
► Toxicogenomics can highlight putative toxicity biomarkers.
► Osteopontin and uranium exposure are associated both in vitro and in vivo.
► A dose–response curve was performed in supernatants of uranium-exposed renal cells.
► Osteopontin was monitored using ELISA in the urine of uranium exposed workers.
► Urinary osteopontin decreases when excreted uranium exceeds 30 μg/L in urine.