Ultrastructural and metabolic changes in osteoblasts exposed to uranyl nitrate

D.R. TASAT; N.S. ORONA; P.M. MANDALUNIS; R.L . CABRINI; A.M.UBIOS

ARCHIVES OF TOXICOLOGY.

Springer-Verlag

Lugar: Alemania; Año: 2006 vol. 81 p. 319 - 326

0340-5761

Exposure to uranium is an occupational hazard to workers who continually handle uranium and an environmental risk to the population at large. Since the cellular and molecular pathways of uranium toxicity in osteoblast cells are still unknown, the aim of the present work was to evaluate the adverse eVects of uranyl nitrate (UN) on osteoblasts both in vivo and in vitro. Herein we studied the osteoblastic ultrastructural changes induced by UN in vivo and analyzed cell proliferation, generation of reactive oxygen species (ROS), apoptosis, and alkaline phosphatase (APh) activity in osteoblasts exposed to various UN concentrations (0.1, 1, 10, and 100 M) in vitro. Cell proliferation was quantiWed by means of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, ROS was determined using the nitro blue tetrazolium test, apoptosis was morphologically determined using Hoechst 3332 and APh activity was assayed spectrophotometrically.Electron microscopy revealed that the ultrastructure of active and inactive osteoblasts exposed to uranium presented cytoplasmic and nuclear alterations. In vitro, 1?100 M UN failed to modify cell proliferation ratio and to induce apoptosis. ROS generation increased in a dose-dependent manner in all tested doses. APh activity was found to decrease in 1?100 M UN-treated cells vs. controls. Our results show that UN modiWes osteoblast cell metabolism by increasing ROS generation and reducing APh activity,suggesting that ROS may play a more complex role in cell physiology than simply causing oxidative damage.