Biomedical subjects

Alexander Pilger

Publications and source records attributed to Alexander Pilger.

8 recordsLinked to original sources

PubMed2005

Chromosomal damage in human diploid fibroblasts by intermittent exposure to extremely low-frequency electromagnetic fields.

Environmental exposure to extremely low-frequency electromagnetic fields (ELF-EMFs) has been implicated in the development of cancer in humans. An important basis for assessing a potential cancer risk due to ELF-EMF exposure is knowledge of biological effects on human cells at the chromosomal level. Therefore, we investigated in the present study the effect of intermittent ELF electromagnetic fields (50 Hz, sinusoidal, 5'field-on/10'field-off, 2-24 h, 1 mT) on the induction of micronuclei (MN) and chromosomal aberrations in cultured human fibroblasts. ELF-EMF radiation resulted in a time-dependent increase of micronuclei, which became significant after 10 h of intermittent exposure at a flux density of 1 mT. After approximately 15 h a constant level of micronuclei of about three times the basal level was reached. In addition, chromosomal aberrations were increased up to 10-fold above basal levels. Our data strongly indicate a clastogenic potential of intermittent low-frequency electromagnetic fields, which may lead to considerable chromosomal damage in dividing cells.

Cells, Cultured↗

PubMed2005

Cell type-specific genotoxic effects of intermittent extremely low-frequency electromagnetic fields.

The issue of adverse health effects of extremely low-frequency electromagnetic fields (ELF-EMFs) is highly controversial. Contradictory results regarding the genotoxic potential of ELF-EMF have been reported in the literature. To test whether this controversy might reflect differences between the cellular targets examined we exposed cultured cells derived from different tissues to an intermittent ELF-EMF (50 Hz sinusoidal, 1 mT) for 1-24h. The alkaline and neutral comet assays were used to assess ELF-EMF-induced DNA strand breaks. We could identify three responder (human fibroblasts, human melanocytes, rat granulosa cells) and three non-responder cell types (human lymphocytes, human monocytes, human skeletal muscle cells), which points to the significance of the cell system used when investigating genotoxic effects of ELF-EMF.

Animals↗

PubMed2005

No cognitive deficits in men formerly exposed to lead.

OBJECTIVES: The objective of the study was to investigate long-term cognitive effects resulting from low to moderate lead exposure below current threshold values. Executive functions, attention, visuospatial and visuomotor functioning in workers formerly exposed to lead were investigated. METHODS: 48 men formerly exposed to lead and with a mean current blood level (PbB) of 5.4 microg Pb/100 ml were investigated, together with 48 matched controls (PbB, 4.7 microg Pb/100 ml) out of a pool of 61 males. The two groups were matched for age, years spent in education, verbal intelligence and gram alcohol consumption per week. The following neuropsychological tests were used: modified Wisconsin card sorting test, block design test, visual recognition test, simple reaction time, choice reaction and digit-symbol substitution. Lead exposure was assessed using both current and cumulative measurements. RESULTS: There were no significant differences in cognitive parameters between the two groups. When analyzing dose-response relationships, negative correlations were found between PbB and performance in the block design test, and between PbB and scores in the visual recognition and digit-symbol substitution tests. High cumulative exposure (IBL, >5000; duration of exposure, >5 years) correlated only with wrong reactions in the choice reaction test. CONCLUSIONS: The results of our study indicate that cognitive deficits resulting from low-level exposure to lead are reversible. The study was limited to low-level long-term exposure (all PbB values were always below 55 microg Pb/100 ml), and extrapolation of these results to persons heavily exposed to lead is not possible.

Adult↗

PubMed2004

No effects of intermittent 50 Hz EMF on cytoplasmic free calcium and on the mitochondrial membrane potential in human diploid fibroblasts.

The recently described increase in DNA strand breaks of cultured human diploid fibroblasts after intermittent exposure to extremely-low-frequency electromagnetic fields (ELF-EMF) of more than about 70 microT ELF-EMF is difficult to explain by a direct induction of covalent bond disruption. Therefore the hypothesis has been tested that ELF-EMF-induced DNA strand breaks might be mediated by cellular processes that cause alteration of the intracellular concentration of free calcium ([Ca2+]i) and/or the membrane potential (DeltaPsi(m)). [Ca2+]i was determined by the ratiometric fura-2 technique. Changes in DeltaPsi(m) were assessed by using the potential-dependent lipophilic cationic probe JC-1. Human fibroblasts were exposed to intermittent ELF-EMF (50 Hz, 1000 microT). Although exposure of fiboblasts to ELF-EMF resulted in a highly significant increase in DNA strand breaks as determined by the comet assay, no effect on JC-1 fluorescence emission or on [Ca2+]i has been observed when comparing exposed with sham-exposed cells. Therefore, it is suggested that ELF-EMF-induced DNA strand breaks are unlikely to be caused by intracellular changes that affect [Ca2+]i and/or DeltaPsi(m).

Calcium↗

PubMed2002

Induction of DNA strand breaks by intermittent exposure to extremely-low-frequency electromagnetic fields in human diploid fibroblasts.

Results of epidemiological research show low association of electromagnetic field (EMF) with increased risk of cancerous diseases and missing dose-effect relations. An important component in assessing potential cancer risk is knowledge concerning any genotoxic effects of extremely-low-frequency-EMF (ELF-EMF). Human diploid fibroblasts were exposed to continuous or intermittent ELF-EMF (50Hz, sinusoidal, 24h, 1000microT). For evaluation of genotoxic effects in form of DNA single- (SSB) and double-strand breaks (DSB), the alkaline and the neutral comet assay were used. In contrast to continuous ELF-EMF exposure, the application of intermittent fields reproducibly resulted in a significant increase of DNA strand break levels, mainly DSBs, as compared to non-exposed controls. The conditions of intermittence showed an impact on the induction of DNA strand breaks, producing the highest levels at 5min field-on/10min field-off. We also found individual differences in response to ELF-EMF as well as an evident exposure-response relationship between magnetic flux density and DNA migration in the comet assay. Our data strongly indicate a genotoxic potential of intermittent EMF. This points to the need of further studies in vivo and consideration about environmental threshold values for ELF exposure.

Adult↗

PubMed2002

Vanadate induces DNA strand breaks in cultured human fibroblasts at doses relevant to occupational exposure.

To study possible genotoxic effects of occupational exposure to vanadium pentoxide, we determined DNA strand breaks (with alkaline comet assay), 8-hydroxy-2'deoxyguanosine (8-OHdG) and the frequency of sister chromatid exchange (SCE) in whole blood leukocytes or lymphocytes of 49 male workers employed in a vanadium factory in comparison to 12 non-exposed controls. In addition, vanadate has been tested in vitro to induce DNA strand breaks in whole blood cells, isolated lymphocytes and cultured human fibroblasts of healthy donors at concentrations comparable to the observed levels of vanadium in vivo. To investigate the impact of vanadate on the repair of damaged DNA, co-exposure to UV or bleomycin was used in fibroblasts, and DNA migration in the alkaline and neutral comet assay was determined. Although, exposed workers showed a significant vanadium uptake (serum: median 5.38microg/l, range 2.18-46.35microg/l) no increase in cytogenetic effects or oxidative DNA damage in leukocytes could be demonstrated. This was consistent with the observation that in vitro exposure of whole blood leukocytes and lymphocytes to vanadate caused no significant changes in DNA strand breaks below concentrations of 1microM (50microg/l). In contrast, vanadate clearly induced DNA fragmentation in cultured fibroblasts at relevant concentrations. Combined exposure of fibroblasts to vanadate/UV or vanadate/bleomycin resulted in non-repairable DNA double strand breaks (DSBs) as seen in the neutral comet assay. We conclude that exposure of human fibroblasts to vanadate effectively causes DNA strand breaks, and co-exposure of cells to other genotoxic agents may result in persistent DNA damage.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2002

Urinary 8-hydroxydeoxyguanosine and sister chromatid exchanges in patients with total hip replacements.

Ion release from metal implants has been suspected to increase the risk of genotoxic effects in patients wearing orthopedic metal devices. In this study we used urinary 8-hydroxydeoxyguanosine (8-OHdG) as marker of oxidative DNA damage and the frequency of sister chromatid exchanges in lymphocytes to test a possible relationship between the concentrations of chromium or cobalt and the induction of cytogenetic modifications in 46 patients with total hip replacements. A broad range of individual levels of metals has been observed in these patients: chromium in blood, 1.59-14.11 microg/L; chromium in urine, 0.79-93.80 microg/24 h; cobalt in blood, 0.77-37.80 microg/L; cobalt in urine, 2.59-166.94 microg/24 h. By linear regression analysis, no significant correlation between urinary 8OHdG or sister chromatid exchange (SCE) and the concentrations of metals was found. However, cobalt in blood as well as 8-OHdG in urine were higher in patients with implants 3-4 yr old as compared to patients with implants 1-2 yr old. Smoking significantly increased the frequency of SCE. Our data do not indicate a dependence of 8-OHdG in urine or SCE on the levels of chromium or cobalt in patients with total hip replacements.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2002

Induction of 8-hydroxy-2'-deoxyguanosine by cobalt(II) and hydrogen peroxide in vitro.

In order to test the effects of cobalt on oxidative DNA damage, we measured the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the presence of cobalt in calf thymus DNA and in DNA of human diploid fibroblasts. Treatment of calf thymus DNA with Co(II) at 500 microM hydrogen peroxide resulted in a dose-dependent increase in 8-OHdG, which culminated at 25 microM Co(II) (62.6 modified/10(5) dG) and declined at higher Co(II) concentrations [9.6 modified/10(5) dG at 250 microM Co(II)]. Incubation of calf thymus DNA with Co(II) alone did not cause an increase in 8-OHdG. Treatment of calf thymus DNA with H2O2, (0.25-2 mM) caused only a slight generation of 8-OHdG (2.7/10(5) dG, at 2 mM H2O2). Exposure of human diploid fibroblasts to Co(II) at 5-250 microM did not result in an increase in 8-OHdG in a dose-dependent manner, although treated cells showed significantly higher 8-OHdG levels than untreated controls (2.026 +/- 0.695 vs. 1.395 +/- 0.433 8-OHdG/10(5) dG) at all concentrations. Our data indicate that in the presence of H2O2, Co(II) stimulates the in vitro formation of 8-OHdG.

8-Hydroxy-2'-Deoxyguanosine↗