Toxicity assessment of tamoxifen by means of a bacterial model

A strain of Bacillus stearothermophilus was used as a model to study physic al perturbations induced in the membrane by the cytostatic tamoxifen (TAM). This study was carried out using two lines of criteria: (1) bacterial grow th, and temperature growth range, with determination of growth parameters a s a function of TAM concentration; and (2) biophysical studies by different ial scanning calorimetry (DSC) and by means of two fluorescent probes to ev aluate perturbations promoted by the drug on the structural order of bacter ial lipid membranes. The inhibition of growth induced by TAM, the structura l bilayer disordering, and the shift in the phase transition temperature to a lower range were also determined in the presence of Ca2+, i.e., a natura l membrane stabilizer, to elucidate further perturbing effects of TAM on me mbranes with putative implications in cell toxicity. Growth inhibition prom oted by TAM is potentiated by an increase in growth temperature above the o ptimal range, but attenuated or relieved by the addition of 2.5 mM Ca2+ to the culture medium. Consistently, fluorescence polarization and DSC studies showed that Ca2+ ions (2.5 mM) effectively compensated for the destabilizi ng effects promoted by TAM in bacterial lipid membranes.