A calorimetric evidence of the interaction and transport of environmentally carcinogenic compounds through biomembranes F. Castelli * , V. Librando, M.G. Sarpietro Dipartimento di Scienze Chimiche, Universita Á di Catania, Viale A. Doria 6, 95125 Catania, Italy Received 15 December 2000; accepted 6 February 2001 Abstract The effect exerted by pyrene and nitro-pyrene N-pyrene), two structurally similar polycyclic aromatic hydrocarbons PAH S ), possessing mutagenic and carcinogenic activity, on the thermotropic behaviour of model membranes constituted by dimyristoylphosphatidylcholine DMPC) vesicles, was investigated by differential scanning calorimetry DSC). Attention was directed to evaluate modi®cations in mutagen±lipid interaction induced by compound structure and lipophily and evidences in their membrane penetration. The two examined compounds, when dispersed in liposomes during their preparation, were found to exert a very different actiononthe L b to L a gel-to-liquidcrystalphasetransitionofDMPCmultilamellarvesiclesMLV).Pyrenecausedadetectable effect on the transition temperature T m ), shifting it towards lower values with a concomitant decrease of the associated enthalpy DH) changes, while N-pyrene was able to modify the lipid vesicles thermotropic behaviour only for low molar fractions, without deep changes in the DH. Modi®cations induced by pyrene were a function of mutagen concentration while thedifferentbehaviourofN-pyrenecanbeduetodifferentpolarityinducedbythepresenceofthenitro-group,whichattribute an higher hydrophilic character. Solid pyrene and N-pyrene and MLVaqueous dispersions 0.12 molar fraction) were left in touch for long incubation times at temperature higher than the transitional temperature of DMPC to detect their spontaneous transfer through the medium. By following this procedure, no interaction was detected for both pyrene and N-pyrene with lipid vesicles, suggesting that their low hydrophilic character avoid their migration through the aqueous layer surrounding the MLV vesicles. Carrying out a kinetic measurement leaving for increasing incubation times charged MLV 0.12molar fraction) with empty DMPC vesicles the uptake of the PAHs by the empty vesicles and their successive interaction, after several periods of incubations, was monitored. Pyrene and N-pyrene showed a different kinetic behaviour: the N-pyrene rate transfer was faster than that of pyrenebutboth®naltransferandinteractionwereonthesameorderthatdetectedbypreparationofMLVchargedwitha0.06 molar fraction of PAH, carried out in organic solvent.The obtained results suggest that the PAH S ,evenifunabletoreachand penetrate the biological membranes migrating through an aqueous layer, when dispersed in a lipophilic medium are able to penetrate and diffuse inside a model membrane. The different effects observed could be explained in terms of compound hydrophobicity and a relation between compound structure and membrane interaction can be suggested. This allows the membraneinteractionwithpyreneforallthetestedmolarfractions,butthestructureofN-pyreneseemstosuggesttheformation of aggregate on the membrane surface for molar fractions higher than 0.09. # 2001 Elsevier Science B.V. All rights reserved. Keywords: Differential scanning calorimetry; Pyrene; Nitro-pyrene; PAH; Phosphatidylcholine; Membranes Thermochimica Acta 373 2001) 133±140 * Corresponding author. Fax: 39-95-580138. E-mail address: fcastelli@dipchi.unict.it F. Castelli). 0040-6031/01/$ ± see front matter # 2001 Elsevier Science B.V. All rights reserved. PII:S0040-603101)00477-4