Use ofBacillus stearothermophilus as a model to study tamoxifen-membrane interactions.
A strain ofBacillus stearothermophilus was used as a model to study the interaction of tamoxifen (TAM) with the cell membrane and the cytostatic antiproliferative effects not related to oestrogen binding. The bacterial growth in the presence of TAM was evaluated turbidimetrically and by viable cell counting. In parallel, partition coefficients of TAM in bacterial polar lipid bilayers were determined. Additionally, studies with fluorescent probes were carried out to investigate TAM effects on the physical state of the membrane lipid bilayer. TAM inhibits growth ofB. stearothermophilus and induces loss of cell viability as a function of concentration and the growth temperature. High partitioning of this drug in the bacterial lipid membranes was observed, reaching maximal values in the temperature range of the phase transition. Fluorescence polarizations of 1,6-diphenyl-1,3,5-hexatriene (DPH) and of 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 behaviour of bacterial membrane lipids is suggested.
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Laborato rio de Microbiologia, Faculdade de Farma cia, Coura; Centro de Neurocie^ncias, Universidade de Coimbra, 3000, Coimbra, Portugal.
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Custo Dio
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