TY - JOUR
T1 - Combinations of chlorocatechols and heavy metals cause DNA degradation in vitro but must not result in increased mutation rates in vivo
AU - Schweigert, Nina
AU - Belkin, Shimshon
AU - Leong-Morgenthaler, Phaik
AU - Zehnder, Alexander J.B.
AU - Eggen, Rik I.L.
PY - 1999
Y1 - 1999
N2 - Chlorocatechols introduced into the environment directly or as a result of degradation processes are highly toxic, particularly when combined with heavy metals. With in vitro DNA degradation assays, the high reactivity of chlorocatechols combined with heavy metals could be shown, whereby copper was shown to be more active than iron. Structure-activity analysis showed that the degradation potential of the chlorocatechols decreased with an increasing number of chloratoms. The addition of reactive oxygen species scavengers allowed the identification of hydrogen peroxide as an important agent leading to DNA damage in this reaction. The potential of other reactive compounds, however, can neither be determined nor excluded with this approach. Exposure of Escherichia coli and Salmonella typhimurium cultures to the same mixtures of chlorocatechols and copper surprisingly did not lead to an enhanced mutation rate. This phenomenon was explained by doing marker gene expression measurements and toxicity tests with E. coli mutants deficient in oxidative stress defense or DNA repair. In catechol-copper-exposed cultures an increased peroxide level could indeed be demonstrated, but the highly efficient defense and repair systems of E. coli avoid the phenotypical establishment of mutations. Increased mutation rates under chronic exposure, however, cannot be excluded.
AB - Chlorocatechols introduced into the environment directly or as a result of degradation processes are highly toxic, particularly when combined with heavy metals. With in vitro DNA degradation assays, the high reactivity of chlorocatechols combined with heavy metals could be shown, whereby copper was shown to be more active than iron. Structure-activity analysis showed that the degradation potential of the chlorocatechols decreased with an increasing number of chloratoms. The addition of reactive oxygen species scavengers allowed the identification of hydrogen peroxide as an important agent leading to DNA damage in this reaction. The potential of other reactive compounds, however, can neither be determined nor excluded with this approach. Exposure of Escherichia coli and Salmonella typhimurium cultures to the same mixtures of chlorocatechols and copper surprisingly did not lead to an enhanced mutation rate. This phenomenon was explained by doing marker gene expression measurements and toxicity tests with E. coli mutants deficient in oxidative stress defense or DNA repair. In catechol-copper-exposed cultures an increased peroxide level could indeed be demonstrated, but the highly efficient defense and repair systems of E. coli avoid the phenotypical establishment of mutations. Increased mutation rates under chronic exposure, however, cannot be excluded.
KW - Chlorocatechol
KW - Copper
KW - DNA damage
KW - Marker gene
KW - Mutation
KW - Reactive oxygen species
KW - Structure-activity
UR - http://www.scopus.com/inward/record.url?scp=0032931488&partnerID=8YFLogxK
U2 - 10.1002/(SICI)1098-2280(1999)33:3<202::AID-EM4>3.0.CO;2-C
DO - 10.1002/(SICI)1098-2280(1999)33:3<202::AID-EM4>3.0.CO;2-C
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C2 - 10334622
AN - SCOPUS:0032931488
SN - 0893-6692
VL - 33
SP - 202
EP - 210
JO - Environmental and Molecular Mutagenesis
JF - Environmental and Molecular Mutagenesis
IS - 3
ER -