Metal-induced Lympho-toxicity Is Not Preferentially Mediated By Dna Damage, Diminishing The Likelihood Of Implant Induced Lymphoma

摘要

The carcinogenic/toxic potential of implant metals remains an area of concern. Initially, epidemiological studies implicated cancer incidence in the first and second decades following total hip replacement.(1) However, larger, more recent studies have found no significant increase in leukemia or lymphoma; although, these studies did not include as large a proportion of subjects with a metal-on-metal prosthesis.(2) While metals have been documented to produce toxic effects at elevated concentrations (3), the carcinogenic potential to peri implant cells, e.g. the ability to preferentially induce DNA damage (mutagenesis) remains unknown. Can soluble implant metals induce DNA damage preferentially to other mechanisms of cellular toxicity? To address this question, we hypothesized that implant metals will be preferentially carcinogenic, i.e. generalized toxicity and/or programmed cell death, apoptosis, will not preferentially affect lymphocytes prior to significant DNA damage. We tested this hypothesis by challenging human T-helper lymphocytes (Jurkat) challenged with an array of soluble implant metals and measuring resultant apoptosis, DNA damage and generalized toxicity (decreased proliferation) responses.