Differential perturbation of erythrocyte membrane function by structurally related polycyclic aromatic hydrocarbons.
Examination of the interaction of a number of structurally related polycyclic aromatic hydrocarbons with the erythrocyte plasma membrane indicated that the presence and position of methyl groups on the lipophilic hydrocarbon nucleus determined whether the compound acted as an inhibitor of membrane function. 7,12-Dimethylbenz(a)anthracene, a potent carcinogen, acted as a noncompetitive inhibitor of membrane acetylcholinesterase. The inhibition depended on the anion composition of the buffer at the time of exposure of the cells to inhibitor, i.e., it was only manifest in the presence of an anion gradient. The temperature dependence of the intact cell enzyme in the presence of inhibitor was influenced by the temperature at which the compound was added prior to assay and may involve the perturbation of tightly associated lipids. Glucose exchange across the membrane was inhibited by the same compounds which inhibit acetylcholinesterase. The temperature dependence of the exchange was not grossly altered by the presence of 7,12-dimethylbenz(a)anthracene. The observed inhibition of two membrane functions by the polycyclic aromatic hydrocarbons does not correlate simply with their theoretical octanol/water partition coefficients, water solubilities, or ability to confer membrane stabilization against osmotic hemolysis. This demonstration of differential inhibition by compounds having the same overall hydrophobicity was unexpected and suggests a more complex mode of interaction with the cell membrane.