USE OF BACILLUS-STEAROTHERMOPHILUS AS A MODEL TO STUDY TAMOXIFEN-MEMBRANE INTERACTIONS

A strain of Bacillus stearothermophilus was used as a model to study t he interaction of tamoxifen (TAM) with the cell membrane and the cytos tatic antiproliferative effects not related to oestrogen binding. The bacterial growth in the presence of TAM was evaluated turbidimetricall y and by viable cell counting. In parallel, partition coefficients of TAM in bacterial polar lipid bilayers were determined. Additionally, s tudies with fluorescent probes were carried out to investigate TAM eff ects on the physical state of the membrane lipid bilayer. TAM inhibits growth of B. stearothermophilus and induces loss of cell viability as a function of concentration and the growth temperature. High partitio ning of this drug in the bacterial lipid membranes was observed, reach ing maximal values in the temperature range of the phase transition. F luorescence polarizations of 1,6-diphenyl-1,3,5-hexatriene (DPH) and o f its propionic acid derivative (DPH-PA) report significant structural disorder of the lipid bilayer induced by the cytostatic, particularly in the phase transition range. A putative relationship between growth impairment by TAM and the TAM-induced perturbation of the physical be haviour of bacterial membrane lipids is suggested. Copyright (C) 1996 Elsevier Science Ltd.