Combinations of chlorocatechols and heavy metals cause DNA degradation in vitro but must not result in increased mutation rates in vivo

• Published in: Environmental and molecular mutagenesis Vol. 33; no. 3; pp. 202 - 210
• Main Authors: Schweigert, Nina, Belkin, Shimshon, Leong-Morgenthaler, Phaik, Zehnder, Alexander J.B., Eggen, Rik I.L.
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 1999; Wiley-Liss
• Subjects: Biological and medical sciences; Catalase - metabolism; Catalase - pharmacology; Catechols - antagonists & inhibitors; Catechols - chemistry; Catechols - pharmacology; Chemical mutagenesis; Chlorine - analysis; Chlorine - pharmacology; chlorocatechol; copper; Copper - antagonists & inhibitors; Copper - pharmacology; DNA damage; DNA Damage - drug effects; DNA Repair - genetics; Dose-Response Relationship, Drug; Escherichia coli - drug effects; Escherichia coli - enzymology; Escherichia coli - genetics; Free Radical Scavengers - pharmacology; Gene Expression Regulation, Bacterial - drug effects; Genes, Bacterial - genetics; Hydrogen Peroxide - metabolism; Iron - pharmacology; marker gene; Medical sciences; Microbial Sensitivity Tests; Models, Chemical; Mutagenesis - drug effects; Mutagenicity Tests; Mutation; Oxidative Stress - genetics; Plasmids - genetics; Plasmids - metabolism; reactive oxygen species; Reactive Oxygen Species - metabolism; Salmonella - drug effects; Salmonella - genetics; structure-activity; Superoxide Dismutase - metabolism; Superoxide Dismutase - pharmacology; Toxicology; Oxidative stress; Pyrocatechol derivatives; Mutagenicity testing; Toxicity; Escherichia coli; In vitro; Salmonella typhimurium; Heavy metal; In vivo; DNA; Bacteria; Mutation; Copper; Enterobacteriaceae
• ISSN: 0893-6692; 1098-2280
• DOI: 10.1002/(SICI)1098-2280(1999)33:3<202::AID-EM4>3.0.CO;2-C

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. Environ. Mol. Mutagen. 33:202–210, 1999 © 1999 Wiley‐Liss, Inc.