Occupational exposure to heavy metals: DNA damage induction and DNA repair inhibition prove co-exposures to cadmium, cobalt and lead as more dangerous than hitherto expected

Abstract

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 ...

Assessment of occupational exposure to welding fumes by inductively coupled plasma‐mass spectroscopy and by the alkaline Comet assay

“…Similar results were reported by Merzenich et al [2001], Palus et al [2003], and Hengstler et al [2003]. As with other carcinogenic metals, Cd could be genotoxic through multiple mechanisms, such as the generation of ROS and the inhibition of DNA repair.…”

“…Two pathways of genotoxicity are possible. The first is the direct or indirect modulation of cellular DNA repair [Hengstler et al, 2003]. The second pathway is based on the modulation of transcriptional factors such as NF-jB and AP-1 [Galaris and Evangelou, 2002].…”

“…In rats, welding fume exposures have been reported to differ from single metal exposures due to synergistic effects of multiple substances . Co-exposure to several metals induced genotoxic effects that exceeded the sum of the effects of single metals [Hengstler et al, 2003]. As stated above, metals could be directly genotoxic by ROS production.…”

Effect of smoking on semen quality, FSH, testosterone level, and CAG repeat length in androgen receptor gene of infertile men in an Indian city

“…It was noted that DNA damage is increased with habitual smoking. There have been previous studies highlighting the induction of DNA damage as well as the inhibition of DNA repair mechanisms by heavy metals [Hengstler et al 2003;Meizel 2004]. A range of molecular mechanisms was proposed, reflective of their diverse chemical properties.…”

“…oxidative DNA damage, strand breaks, and induce mutations [Hengstler et al 2003]. A decrease in repair capacity may increase susceptibility to reactive oxygen species generated by these heavy metals [Hengstler et al 2003].…”