title: Free radicals generated by tantalum implants antagonize the cytotoxic effect of doxorubicin.
abstract: Little is known about the interaction between antineoplastic drugs and implants in bone cancer patients. We investigated the interaction between commercially available porous tantalum (Ta) implants and the chemotherapeutic drug, Doxorubicin (DOX). DOX solutions were prepared in the presence of Ta implant. The changes in fluorescence intensity of the DOX chromophore were measured by spectrofluorometry and the efficacy of DOX was evaluated by viability of rabbit rectal tumor cells (VX2). After 5 min interaction of the DOX solution (5 μg/ml) with the Ta implant, the fluorescent intensity of the DOX solution was 85% degraded, and only 20% the drug efficacy to kill VX2 cells was retained. However, after adding a reducing agent, Dithiothreitol (DTT, 10 μg/ml), 80% of the original fluorescence and 50% of the drug efficacy were restored while UV irradiation enhanced drug degradation in the presence of Ta implant. The action of DTT and UV irradiation indicated that reactive oxygen species (ROS) were involved in the drug degradation mechanism. We detected that Ta implants in aqueous medium produced hydroxyl radicals. Cells showed higher intracellular ROS activity when culture medium was incubated with the Ta implant prior to cell culture. It is concluded that the porous Ta implant antagonizes the cytotoxicity of DOX via ROS generation of the porous Ta implant.
authors.affiliation: Orthopaedic Research Lab, Aarhus University Hospital, 8000 Aarhus C, Denmark. chen.muwan@ki.au.dk
authors.forename: Muwan
authors.initials: M
authors.lastname: Chen
authors.forename: San
authors.initials: S
authors.lastname: Hein
authors.forename: Dang Q S
authors.initials: DQ
authors.lastname: Le
authors.forename: Wenzhou
authors.initials: W
authors.lastname: Feng
authors.forename: Morten
authors.initials: M
authors.lastname: Foss
authors.forename: Jørgen
authors.initials: J
authors.lastname: Kjems
authors.forename: Flemming
authors.initials: F
authors.lastname: Besenbacher
authors.forename: Xuenong
authors.initials: X
authors.lastname: Zou
authors.forename: Cody
authors.initials: C
authors.lastname: Bünger
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000737:chemistry* / Q000494:pharmacology / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004229:Dithiothreitol / Q000494:pharmacology; D004317:Doxorubicin / Q000737:chemistry* / Q000494:pharmacology / Q000528:radiation effects; D019736:Prostheses and Implants; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000737:chemistry* / Q000378:metabolism; D013635:Tantalum / Q000737:chemistry*; D014466:Ultraviolet Rays
chemical_list: D000903:Antibiotics, Antineoplastic; D017382:Reactive Oxygen Species; D013635:Tantalum; D004317:Doxorubicin; D004229:Dithiothreitol