Lakowicz J R, Bevan D R
Biochemistry. 1979 Nov 13;18(23):5170-6. doi: 10.1021/bi00590a022.
Particulate matter and polynuclear aromatic hydrocarbons are known to be cocarcinogenic. Using fluorescence spectroscopy, we determined that adsorption of benzoic] pyrene (BP) to iron oxide, silica, and asbestos (anthophyllite and Canadian chrysotile) results in a greatly enhanced rate of BP uptake into rat liver microsomes when compared to uptake from aqueous dispersions of BP microcrystals. Simple mixtures of BP microcrystals and particulates do not display enhanced microsomal uptake rates, an observation which indicates that adsorption of BP to the surface of the particle is necessary for enhanced microsomal uptake. BP was not released into microsomes from carbon black. Most importantly, the data indicate that asbestos particles are more effective than silica and iron oxide in enhancing the microsomal availability of BP. These observations suggest that particles, and especially the fibrous mineral particulates, could be cocarcinogenic as a result of their ability to adsorb polynuclear aromatic hydrocarbons and to transport these carcinogens into cells. Except for chrysotile, the particles did not disrupt microsomal integrity as determined by NADPH-dependent lipid peroxidation activity. Binding of the microsomes to the particles did not affect the BP uptake rates. In addition, these BP uptake rates were independent of both the concentrations of microsomes and of particles. These observations are consistent with the mechanism of particle-enhanced transport being an increased rate of BP solubilization from the adsorbed state into the aqueous phase, followed by rapid partitioning of BP into the microsomal membranes.
已知颗粒物和多环芳烃具有协同致癌性。利用荧光光谱法,我们测定了苯并[a]芘(BP)吸附到氧化铁、二氧化硅和石棉(直闪石和加拿大温石棉)上后,与从BP微晶的水分散体摄取相比,其被大鼠肝微粒体摄取的速率大大提高。BP微晶和颗粒物的简单混合物并未显示出微粒体摄取速率的提高,这一观察结果表明,BP吸附到颗粒表面是微粒体摄取增强所必需的。BP未从炭黑释放到微粒体中。最重要的是,数据表明石棉颗粒在提高BP的微粒体可利用性方面比二氧化硅和氧化铁更有效。这些观察结果表明,颗粒,尤其是纤维状矿物颗粒,可能因其吸附多环芳烃并将这些致癌物转运到细胞中的能力而具有协同致癌性。除温石棉外,通过NADPH依赖性脂质过氧化活性测定,颗粒并未破坏微粒体完整性。微粒体与颗粒的结合并不影响BP摄取速率。此外,这些BP摄取速率与微粒体和颗粒的浓度均无关。这些观察结果与颗粒增强转运的机制一致,即BP从吸附状态溶解到水相中的速率增加,随后BP迅速分配到微粒体膜中。