Analysis of lipophilic carcinogen-membrane interactions using a model human erythrocyte membrane system

Human erythrocytes have been used as a model for evaluating the chemical carcinogen-plasma membrane interaction. The carcinogenic aromatic amines 2-acetylaminofluorene, dimethylaminoazobenzene, and 3'-methyldimethylaminoazobene stabilize erythrocytes against lysis in hypotonic solution. In general, the stabilization potential of these compounds reflects their oil:water partition coefficients and may be related to both their extracellular distribution and ultimate capacity for penetration of target cells. The polycyclic aromatic hydrocarbons, 3-methylcholanthrene and benz[a]anthracene, confer little protection against hemolysis and simultaneous incubation of nonprotective 3-methylcholanthrene and protective 3'-methyldimethylaminoazobenzene slightly alters the stabilization afforded by the latter. 7,12-dimethylbenz[a]anthracene exhibits greater protective capacity than does benz[a]anthracene. Polycyclic aromatic hydrocarbons manifested considerably higher degrees of absolute binding to erythrocytes in isotonic solution than did aromatic amines. The difference in erythrocyte binding and stabilization exhibited by the 2 classes of carcinogens suggest distinct mechanisms of membrane association that may relate to their metabolic disposition.