Monteiro J P, Martins J D, Luxo P C, Jurado A S, Madeira V M C
Centro de Neurociências, Universidade de Coimbra, 3000 Coimbra, Portugal.
Toxicol In Vitro. 2003 Oct-Dec;17(5-6):629-34. doi: 10.1016/s0887-2333(03)00111-5.
A strain of the thermophilic eubacterium Bacillus stearothermophilus was used as a model system to identify membrane mediated cytotoxic effects of 4-hydroxytamoxifen, following previous studies with tamoxifen. With this experimental approach we attempted to further clarify tamoxifen and 4-hydroxytamoxifen membrane interactions often evoked as responsible for their multiple cellular effects. Bacterial growth and the oxygen consumption rate provided quantitative data of the cytotoxic action of hydroxytamoxifen. The effects of hydroxytamoxifen on the physical properties of bacterial lipid membrane preparations were also evaluated by fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene. Cultures of B. stearothermophilus grown in a complex medium containing hydroxytamoxifen in the concentration range of 1 to 7 microM exhibited progressively longer lag adapting periods, decreased specific growth rates and lower growth yields, as compared to control cultures. Hydroxytamoxifen also affected the electron redox flow of B. stearothermophilus protoplasts and induced significant perturbation of the structural order of bacterial lipid dispersions. We concluded that the bacterial model provides useful information about the nature and repercussion of membrane physical interactions of this lipophilic drug, on the basis of an easy and economic methodology.
在先前对他莫昔芬进行研究之后，一种嗜热真细菌嗜热脂肪芽孢杆菌被用作模型系统，以确定4-羟基他莫昔芬的膜介导细胞毒性作用。通过这种实验方法，我们试图进一步阐明他莫昔芬和4-羟基他莫昔芬的膜相互作用，这种相互作用常被认为是其多种细胞效应的原因。细菌生长和耗氧率提供了羟基他莫昔芬细胞毒性作用的定量数据。还通过1,6-二苯基-1,3,5-己三烯的荧光偏振评估了羟基他莫昔芬对细菌脂质膜制剂物理性质的影响。与对照培养物相比，在含有浓度范围为1至7 microM羟基他莫昔芬的复合培养基中生长的嗜热脂肪芽孢杆菌培养物表现出逐渐延长的适应延迟期、降低的比生长速率和较低的生长产量。羟基他莫昔芬还影响嗜热脂肪芽孢杆菌原生质体的电子氧化还原流，并引起细菌脂质分散体结构顺序的显著扰动。我们得出结论，基于一种简单且经济的方法，该细菌模型提供了有关这种亲脂性药物膜物理相互作用的性质和影响的有用信息。
