Synergistic DNA damage by oxidative stress (induced by H2O2) and nongenotoxic environmental chemicals in human fibroblasts.
Genotoxic combination effects of oxidative stress (induced by H2O2) and eight nongenotoxic environmental chemicals (4-chloroaniline, 2,3,4,6-tetrachlorophenol, lindane, 2,4-dichloroacetic acid (2,4-D), m-xylene, glyphosate, nitrilotriacetic acid and n-hexanol) were determined in human fibroblasts. Genotoxicity was measured quantitatively by the single cell gel electrophoresis assay. The nongenotoxic chemicals were used in non cytotoxic concentrations. H2O2 was used in concentrations producing low (50 microM) and no cytotoxicity (40 microM). All environmental chemicals acted in a synergistic way with H2O2 except DMSO which effectively inhibited H2O(2)-induced DNA damage. The most effective enhancers were 4-chloroaniline, 2,3,4,6-tetrachlorophenol, m-xylene, and n-hexanol. Synergistic effects of hexanol/H2O2 were still evident at a concentration of 0.09 noec (no observed effect concentration). In contrast to synergistic DNA damage in the cell antagonism was found measuring DNA breakage in isolated PM2 DNA. From the results we concluded that synergisms between H2O2 and nongenotoxic chemicals may be a general phenomenon which is not observed on the level of isolated DNA.
Lueken
A
A
Carl von Ossietzky Universität Oldenburg, Fak. V, Institute of Biology and Environm. Sciences, Postfach 2503, D-26111, Oldenburg, Germany.
Juhl-Strauss
U
U
Krieger
G
G
Witte
I
I
D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004785:Environmental Pollutants / Q000633:toxicity*; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*; D009153:Mutagens / Q000633:toxicity*; D018384:Oxidative Stress
D004785:Environmental Pollutants; D009153:Mutagens; D006861:Hydrogen Peroxide