Correlation of synergistic cytotoxic effects of environmental chemicals in human fibroblasts with their lipophilicity.
The cytotoxic combination effects of 2,4-D with 12 xenobiotics having different lipophilicity were investigated in human fibroblasts at their no effect concentrations (NOEC). Each of the chemicals tested in binary combinations enhanced the toxicity of 2,4-D. These synergistic combination effects were independent of the chemical structure of the test compounds. However, the NOEC's of the xenobiotics used in the combinations varied by a factor of 10,000. For strongly lipophilic compounds the lowest NOEC's were needed to induce synergistic cytotoxicity. A linear regression analysis of the concentrations (NOEC's) of the 12 combined xenobiotics against their lipophilicity revealed a correlation with r = 0.96 for 11 agents. This close correlation may be explained by the membrane damaging properties of lipophilic compounds which enhance the uptake of hydrophilic agents.
Witte
I
I
Carl von Ossietzky Universität Oldenburg.
Jacobi
H
H
Juhl-Strauss
U
U
D015084:2,4-Dichlorophenoxyacetic Acid / Q000633:toxicity*; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D004357:Drug Synergism; D005347:Fibroblasts; D006540:Herbicides / Q000633:toxicity*; D006801:Humans; D016014:Linear Models; D008055:Lipids / Q000737:chemistry*; D008452:Maximum Allowable Concentration; D019055:No-Observed-Adverse-Effect Level; D015262:Xenobiotics / Q000737:chemistry / Q000633:toxicity*
D006540:Herbicides; D008055:Lipids; D015262:Xenobiotics; D015084:2,4-Dichlorophenoxyacetic Acid