Co-exposure to cadmium, cobalt, lead and other heavy metals occurs in many occupational settings, such as pigment and batteries production, galvanization and recycling of electric tools. However, little is known about interactions between several heavy metals. In the present study we determined DNA single strand break (DNA-SSB) induction and repair capacity for 8-oxoguanine in mononuclear blood cells of 78 individuals co-exposed to cadmium (range of concentrations in air: 0.05-138.00 micro g/m(3)), cobalt (range: 0-10 micro g/m(3)) and lead (range: 0-125 micro g/m(3)). Exposure to heavy metals was determined in air, blood and urine. Non-parametric correlation analysis showed a correlation between cadmium concentrations in air with DNA-SSB (P = 0.001, R = 0.371). Surprisingly, cobalt air concentrations correlated even better (P < 0.001, R = 0.401), whereas lead did not correlate with DNA-SSB. Logistic regression analysis including 11 possible parameters of influence resulted in a model showing that cobalt in air, cadmium in air, cadmium in blood and lead in blood influence the level of DNA-SSB. The positive result with cobalt was surprising, since exposure levels were much lower compared with the TRK-value of 100 micro g/m(3). To examine, whether the positive result with cobalt is stable, we applied several logistic regression models with two blocks, where all factors except cobalt were considered preferentially. All strategies resulted in the model described above. Logistic regression analysis considering also all possible interactions between the relevant parameters of influence finally resulted in the following model: Odds ratio = 1.286(Co in air) x 1.040(Cd in air) x 3.111(Cd in blood) x 0.861(Pb in air) x 1.023(Co in air x Pb in air). This model correctly predicts an increased level of DNA-SSB in 91% of the subjects in our study. One conclusion from this model is the existence of more than multiplicative effects for co-exposures of cadmium, cobalt and lead. For instance increasing lead air concentrations from 1.6 to 50 micro g/m(3) in the presence of constant exposures to cobalt and cadmium (8 micro g/m(3) and 3.8 micro g/m(3)) leads to an almost 5-fold increase in the odds ratio, although lead alone does not increase DNA-SSB. The mechanism behind these interactions might be repair inhibition of oxidative DNA damage, since a decrease in repair capacity will increase susceptibility to reactive oxygen species generated by cadmium or cobalt. Indeed, repair of 8-oxoguanine decreased with increasing exposures and inversely correlated with the level of DNA-SSB (P = 0.001, R = -0.427). Protein expression patterns of individuals exposed to cobalt concentrations of approximately 10 micro g/m(3) were compared with those of unexposed individuals using two-dimensional gel electrophoresis. Qualitative and apparent quantitative alterations in protein expression were selective and certainly occurred in <0.1% of all proteins. In conclusion, the hazard due to cobalt exposure - that has been classified only as IIB by the IARC ...
In the above article, we did not include a GEO accession number for the gene expression data from our study. The expression data can be accessed under the accession number GSE47353 at http://www.ncbi.nlm.nih.gov/geo/. In addition, all data used in our analyses can be obtained at http://chi.nhlbi.nih.gov.
Peroxidative damage induced by reactive oxygen species (ROS) has been proposed as one of the major causes of defective sperm function. The ROS detected in semen reflect an imbalance between ROS generation and degradation. The objective of the present study was to investigate the relationship between the oxidative and anti-oxidative potential in semen of infertile patients and healthy donors. Specimens were obtained from 28 patients and 18 healthy donors (controls). A conventional spermiogram, measurement of luminol-chemiluminescence (CL) in washed semen, and high performance liquid chromatography determination of ascorbic acid and urate concentrations in seminal plasma were performed. Oligozoospermic patients exhibited higher CL signals than controls (P < 0.001). Normozoospermic patients showed lower ascorbic acid (mean +/- SE: 491 +/- 46 microM, P < 0.04) and urate concentrations (320 +/- 22 microM, P < 0.009) than controls (612 +/- 35 and 426 +/- 26 microM respectively). Seminal plasma ascorbic acid was negatively correlated with the CL signals (P < 0.0006) and positively correlated with the percentage of spermatozoa with normal morphology (P < 0.006). This is the first report of a correlation between the anti-oxidant ascorbic acid in seminal plasma and ROS generation in human semen. Furthermore, the reduced ascorbic acid/urate concentrations found in semen of normozoospermic patients might be indicative of a reduced anti-oxidative protection.
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