Carcinogenesis, Vol 19, 2021-2029, Copyright © 1998 by Oxford University Press
M De Boeck, D Lison and M Kirsch-Volders
The mechanisms of cobalt-induced pulmonary interstitial fibrosis and cancer
are incompletely understood. DNA damage, either induced by genotoxic
(direct or via oxygen radicals) or co-genotoxic (e.g. inhibition of DNA
repair) processes may play an important role in the initiation of cancer.
The alkaline comet assay provides a sensitive tool to investigate these two
processes. Cobalt metal, a mixture of cobalt with tungsten carbide and
cobalt chloride, were compared for their DNA-damaging capacity.
Concentrations from 0 to 6.0 microg Co- equivalent/ml were tested. All
three compounds were able to induce DNA damage in isolated human
lymphocytes from three donors, in a dose- and time-dependent way. A
relatively large interexperimental and interdonor variability in response
was observed. This was ascribed to technical parameters and unidentified
individual factors. This confirms the importance of repeating experiments
using the same and different donors. The DNA-damaging potential of the
cobalt-tungsten carbide mixture was higher than that of cobalt metal and
cobalt chloride, which had comparable responses. No significant increase of
DNA migration was observed when the DNA of cells treated with cobalt metal,
cobalt- tungsten carbide or tungsten carbide were incubated with the
oxidative lesion-specific enzyme formamidopyrimidine DNA glycosylase. This
suggests that during the short treatment period no substantial oxidative
damage to DNA was produced. Cobalt metal was able to inhibit the repair of
methylmethanesulphonate-induced DNA damage. This was concluded from
simultaneous exposure to cobalt and methyl methanesulphonate,
post-incubation and post-treatment with 1.2 microg/ml cobalt of methyl
methanesulphonate-treated cells.
ARTICLES
Evaluation of the in vitro direct and indirect genotoxic effects of cobalt compounds using the alkaline comet assay. Influence of interdonor and interexperimental variability
Laboratorium voor Cellulaire Genetica, Vrije Universiteit Brussel, Brussels, Belgium. mdboeck@vub.ac.be
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