Assessment of membrane toxicity using [(3)H]arachidonic acid release in U937 cells

The release of arachidonic acid (AA) from membrane phospholipids is part of a signal system with which cells respond to environmental changes of various kinds. Using the promonocytic cell line U937, the kinetics of AA release was studied in [(3)H]AA-labelled U937 cells under the influence of various chemicals. Membrane-toxic agents such as lysolecithin and sodium dodecyl sulfate (SDS) cause pronounced enhancement of [(3)H]AA release in U937 cells. The effect occurred immediately after exposure and proved to be dose-dependent, non-enzymatic and irreversible. With regard to mean [(3)H]AA-releasing rate in untreated U937 cells, the following maximum tolerable concentrations were found: lysolecithin, 0.5 mug/ml; SDS, 2 mug/ml; dimethoate, 31.3 mug/ml; chloramine, 160 mug/ml; 2,4-dichlorophenoxyacetic acid (2,4-D), 1 mg/ml; formamide, 50 mg/ml and dimethyl sulfoxide, 100 mg/ml. AA release represents a highly sensitive bioindicator for the membrane-toxic effect of a chemical substance.