Long G J, Rosen J F, Pounds J G
Department of Applied Science, Brookhaven National Laboratory, Upton, New York 11973.
Toxicol Appl Pharmacol. 1990 Feb;102(2):346-61. doi: 10.1016/0041-008x(90)90032-p.
A knowledge of bone lead metabolism is critical for understanding the toxicological importance of bone lead, as a toxicant both to bone cells and to soft tissues of the body, as lead is mobilized from large reservoirs in hard tissues. To further understand the processes that mediate metabolism of lead in bone, it is necessary to determine lead metabolism at the cellular level. Experiments were conducted to determine the intracellular steady-state 210Pb kinetics in cultures of primary and clonal osteoblastic bone cells. Osteoblastic bone cells obtained by sequential collagenase digestion of mouse calvaria or rat osteosarcoma (ROS 17/2.8) cells were labeled with 210Pb as 5 microM lead acetate for 20 hr, and kinetic parameters were determined by measuring the efflux of 210Pb from the cells over a 210-min period. The intracellular metabolism of 210Pb was characterized by three kinetic pools of 210Pb in both cell types. Although the values of these parameters differed between the primary osteoblastic cells and ROS cells, the profile of 210Pb was remarkably similar in both cell types. Both types exhibited one large, slowly exchanging pool (S3), indicative of mitochondrial lead. These data show that primary osteoblastic bone cells and ROS cells exhibit similar steady-state lead kinetics, and intracellular lead distribution. These data also establish a working model of lead kinetics in osteoblastic bone cells and now permit an integrated view of lead kinetics in bone.
了解骨铅代谢对于理解骨铅的毒理学重要性至关重要,因为当铅从硬组织中的大量储存库中释放出来时,它对骨细胞和身体软组织都是一种毒物。为了进一步了解介导骨中铅代谢的过程,有必要在细胞水平上确定铅代谢情况。进行了实验以确定原代和成骨细胞系骨细胞培养物中的细胞内稳态210Pb动力学。通过对小鼠颅骨或大鼠骨肉瘤(ROS 17/2.8)细胞进行连续胶原酶消化获得的成骨细胞系骨细胞,用5 microM醋酸铅作为210Pb标记20小时,并通过在210分钟内测量210Pb从细胞中的流出量来确定动力学参数。两种细胞类型中210Pb的细胞内代谢均由三个210Pb动力学池来表征。尽管这些参数的值在原代成骨细胞和ROS细胞之间有所不同,但两种细胞类型中210Pb的概况非常相似。两种类型均表现出一个大的、缓慢交换的池(S3),表明是线粒体铅。这些数据表明原代成骨细胞系骨细胞和ROS细胞表现出相似的稳态铅动力学和细胞内铅分布。这些数据还建立了成骨细胞系骨细胞中铅动力学的工作模型,现在可以对骨中的铅动力学有一个综合的认识。