title: Gadolinium inhibits thymidine incorporation and induces apoptosis in chondrocytes.
abstract: Magnetic resonance arthrography. a procedure where contrast agents containing gadolinium are administered intra-articularly, has become a useful tool in musculoskeletal diagnosis. Although considered safe for systemic use, toxicities in some tissues have been identified for both free gadolinium ion and the gadolinium chelates used as contrast. In this study, the effects of short-term exposure of articular chondrocytes to gadolinium contrast were examined by assaying for proteoglycan synthesis, cell proliferation, and apoptosis. Bovine chondrocytes were grown in monolayer culture and exposed to gadodiamide for 16 h. Proteoglycan synthesis was measured through incorporation of radiolabeled sulfate. Uptake of radiolabeled thymidine assessed cell proliferation. Apoptosis was detected using the TUNEL assay, where DNA strand breaks characteristic of apoptosis are labeled with fluorescent nucleotide. Proteoglycan synthesis was stimulated by lower dose exposure to gadodiamide. At higher doses, proteoglycan synthesis returned to baseline. Cell proliferation decreased following exposure to gadodiamide in a dose-dependent manner. Chondrocyte apoptosis was induced in a dose-dependent manner. Further work is needed to determine if these in vitro effects are present in the intact joint.
authors.affiliation: Department of Orthopaedics, Brown University and Rhode Island Hospital, Providence 02903 USA.
authors.forename: J K
authors.initials: JK
authors.lastname: Greisberg
authors.forename: J M
authors.initials: JM
authors.lastname: Wolf
authors.forename: J
authors.initials: J
authors.lastname: Wyman
authors.forename: L
authors.initials: L
authors.lastname: Zou
authors.forename: R M
authors.initials: RM
authors.lastname: Terek
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002358:Cartilage, Articular / Q000166:cytology; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005682:Gadolinium / Q000633:toxicity*; D011509:Proteoglycans / Q000096:biosynthesis; D013936:Thymidine / Q000493:pharmacokinetics*; D014316:Tritium
chemical_list: D011509:Proteoglycans; D014316:Tritium; D005682:Gadolinium; D013936:Thymidine