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.
D015073:2-Acetylaminofluorene / Q000494:pharmacology; D001551:Benz(a)Anthracenes / Q000494:pharmacology; D001580:Benzopyrenes / Q000494:pharmacology; D002273:Carcinogens / Q000378:metabolism / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects*; D002463:Cell Membrane Permeability; D004347:Drug Interactions; D004912:Erythrocytes / Q000648:ultrastructure; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008242:Lysogeny / Q000187:drug effects; D008748:Methylcholanthrene / Q000494:pharmacology; D008954:Models, Biological; D004124:p-Dimethylaminoazobenzene / Q000494:pharmacology
D001551:Benz(a)Anthracenes; D001580:Benzopyrenes; D002273:Carcinogens; D008748:Methylcholanthrene; D015073:2-Acetylaminofluorene; D004124:p-Dimethylaminoazobenzene