title: Cytotoxic and phenotypic effects of uranium and lead on osteoblastic cells are highly dependent on metal speciation.
abstract: Bone is one of the main retention organs for uranium (U) and lead (Pb). The clinical effects of U or Pb poisoning are well known: acute and chronic intoxications impair bone formation. However, only few studies dealt with the cellular and molecular mechanisms of their toxicity. The purpose of this study was to investigate acute cytotoxicity of U and Pb and their phenotypic effects on rat and human osteoblasts, the cells responsible for bone formation. The most likely species of the toxicants in contact with cells after blood contamination were selected for cell exposure. Results showed that the cytotoxic effect of U and Pb is highly dependent on their speciation. Thus, Pb was cytotoxic when left free in the exposure medium or when complexed with carbonate, cysteine or citrate, but not when complexed with albumin or phosphate, under an insoluble form. U was cytotoxic whatever its speciation, but differences in sensitivity were observed as a function of speciation. Population growth recovery could be obtained after exposure to low doses of U or Pb, except for some U-carbonate complexes which had irreversible effects whatever the dose. The activation of two markers of bone formation and mineralization, osteocalcin and bone sialoprotein (BSP), was observed after exposure to non-toxic doses or non-toxic species of U or Pb while their inhibition was observed after toxic exposure to both metals. This work provides new elements to better understand the complex mechanisms of U and Pb toxicity to osteoblasts. Our results also illustrate the importance of a strictly controlled speciation of the metals in toxicological studies.
authors.affiliation: Laboratoire Pierre Süe, Toxicologie Humaine et Environnementale, CEA-CNRS UMR 9956, Gif-sur-Yvette F91191, France. sarah.milgram@gmail.com
authors.forename: S
authors.initials: S
authors.lastname: Milgram
authors.forename: M
authors.initials: M
authors.lastname: Carrière
authors.forename: C
authors.initials: C
authors.lastname: Thiebault
authors.forename: L
authors.initials: L
authors.lastname: Malaval
authors.forename: B
authors.initials: B
authors.lastname: Gouget
mesh_terms: D000818:Animals; D002113:Calcification, Physiologic / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D006801:Humans; D007854:Lead / Q000737:chemistry / Q000633:toxicity*; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D015675:Osteocalcin / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D010641:Phenotype; D051381:Rats; D012795:Sialoglycoproteins / Q000187:drug effects / Q000378:metabolism; D017974:Uranium Compounds / Q000737:chemistry / Q000633:toxicity*
chemical_list: D012795:Sialoglycoproteins; D017974:Uranium Compounds; D015675:Osteocalcin; D007854:Lead