Removal of xenobiotic dichalorostearic acid from phospholipids and neutrallipids in cultured human cell lines by beta-oxidation and secretion of dichloromyristic acid

Chlorinated fatty acids represent a recently discovered group of potentiall y hazardous organochlorine pollutants in the environment. The ability of hu man cells to incorporate and metabolise this type of fatty acids has never been investigated. The aim of the present study was, therefore, to investig ate if two human cell lines, INT 407 and SH-SY5Y, incorporate and metabolis e extracellular dichlorostearic acid. Cells were incubated with 9,10-dichlo rostearic acid for 24 hr, and the amounts of chlorinated fatty acids in cel ls and culture medium analysed every two days for up to 6 or 10 days. Lipid s were separated by solid phase extraction, transesterified to fatty acid m ethyl esters, and analysed by gas chromatography in combination with a halo gen specific detector (GC/XSD). Dichlorostearic acid, dichloropalmitic acid and dichloromyristic acid were found in phospholipids and in neutral lipid s of the INT 407 cells. Both cell lines secreted considerable amounts of di chloromyristic acid into the culture medium. Cellular or secreted metabolit es shorter than dichloromyristic acid were not Found. Taken together, the r esults suggest that human cells may(I) incorporate chlorinated fatty acids into membrane lipids and storage lipids, (2) metabolise cellular dichlorost earic acid to dichloropalmitic acid and dichloromyristic acid by beta -oxid ation; but that further metabolism is hindered, possibly because of the chl orine atoms, and (3) remove formed dichloromyristic acid by secretion. The removal of cellular dichloromyristic acid might represent an important cell ular defence mechanism and deserves further investigations.