LIPID-COMPOSITION CHANGES INDUCED BY TAMOXIFEN IN A BACTERIAL MODEL SYSTEM

A putative relationship between growth impairment of Bacillus stearoth ermophilus by tamoxifen (TAM) and TAM-induced perturbation of the phys ical properties of bacterial membrane lipids has been observed. The su pplementation of the growth medium with Ca2+ (a membrane stabilizer) p artially relieves growth inhibition by TAM, allowing growth at TAM con centrations that fully impair growth in the basal medium. B. stearothe rmophilus modifies the membrane lipid composition in response to the a ddition of TAM to the growth medium and the response is sensitive to C a2+. Changes in lipid composition are observed in the acyl chains and in the polar head groups of phospholipids. The physical effects of alt eration in these lipids was studied by fluorescence polarization of DP H and DPH-PA. Polar lipid dispersions from TAM-adapted cells grown in a Ca2+ medium show a shift of T-m to higher temperatures and a signifi cant increase of the structural order as compared to lipids from contr ol cells, suggesting that TAM-induced lipid composition changes compen sate for the destabilizing effects of the cytostatic on membrane organ ization, The polar lipids from cells grown in the basal medium contain ing tamoxifen are also altered, but these alterations do not promote o rder increase of the bilayer in spite of a deviation of T-m to higher temperatures as detected by DPH. Data indicate that B. stearothermophi lus controls the membrane lipid composition in response to tamoxifen, to compensate for TAM-promoted disordering in membranes and to provide an appropriate packing of phospholipid molecules in a stable bilayer, putatively disturbed by TAM incorporation. (C) 1998 Elsevier Science B.V.