Correlation between the lipophilicity of substituted phenols and their inhibition of the Na+/K+-ATPase of Chinese hamster ovary cells.
The Na+/K+-ATPase of Chinese Hamster Ovary (CHO) cells, a plasma membrane bound protein was used as a test system to evaluate the toxicity of several phenol derivatives on membranes. Taking only 2 physico-chemical parameters into consideration, viz., the logarithm of the octanol/water partition coefficient as an indicator for the lipophilicity and the sigma-Hammett constant as a measure for the polarity of the phenol substitutes, it was possible to predict the toxicity with high significance. A multivariate regression analysis calculated a correlation coefficient of 0.99. The results confirm studies performed in our laboratory on cytotoxicity and on functional membrane proteins of fungal and mammalian cells [1,2], suggesting a common mechanism of toxicity by the action of hydrophobic xenobiotics on biomembranes. Taking into account the different sensitivities of the test systems, Quantitative Structure-Activity Relationship (QSAR) analyses could help to explain the basic toxicity of several classes of environmental chemicals.
Cascorbi
I
I
Freie Universitat Berlin, Institut für Biochemie und Molekularbiologie, F.R.G.
Ahlers
J
J
D000818:Animals; D002462:Cell Membrane / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D010636:Phenols / Q000494:pharmacology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D012995:Solubility; D013329:Structure-Activity Relationship
D010636:Phenols; D000254:Sodium-Potassium-Exchanging ATPase