Mankin H J, Lippiello L
Arthritis Rheum. 1979 Jun;22(6):579-85. doi: 10.1002/art.1780220604.
Metabolic alterations in immature rabbit joint tissue were examined following in vitro and in vivo exposure to the alkylating agents Thiotepa and nitrogen mustard. Brief exposure in vitro to either agent resulted in marked suppression of incorporation of radiolabeled precursors of protein, RNA, and glycosaminoglycan synthesis in articular cartilage, which was partially reversible after Thiotepa exposure. In vivo, nitrogen mustard has little effect on synovium and transient inhibitory effects on cartilage vital processes, whereas Thiotepa caused a prolonged inhibition of synovial metabolism with little effect on cartilage. Autoradiographic localization of labeled agents indicated that synovial tissue and cartilage were readily penetrated by nitrogen mustard, but only a few synovial lining cells and superficial chondrocytes were labeled with 35S-Thiotepa. Furthermore, trypsin significantly reduced labeling of cartilage with 14C-nitrogen mustard. These data suggest that alkylating agents differentially affect metabolic processes in joint tissues in vivo and that with Thiotepa, this interference occurs primarily in the synovium. The degree of interference is apparently dependent upon the time of exposure to the agents and the relative DNA-RNA synthetic activity of the joint tissue.
在体外和体内将未成熟兔关节组织暴露于烷化剂噻替派和氮芥后，对其代谢变化进行了检查。在体外短暂暴露于任何一种试剂都会导致关节软骨中放射性标记的蛋白质、RNA和糖胺聚糖合成前体的掺入受到明显抑制，在噻替派暴露后这种抑制部分可逆。在体内，氮芥对滑膜几乎没有影响，对软骨重要过程有短暂的抑制作用，而噻替派会导致滑膜代谢的长期抑制，对软骨影响较小。标记试剂的放射自显影定位表明，氮芥很容易穿透滑膜组织和软骨，但只有少数滑膜衬里细胞和表层软骨细胞被35S-噻替派标记。此外，胰蛋白酶显著减少了14C-氮芥对软骨的标记。这些数据表明，烷化剂在体内对关节组织的代谢过程有不同影响，对于噻替派，这种干扰主要发生在滑膜中。干扰程度显然取决于暴露于试剂的时间以及关节组织相对的DNA-RNA合成活性。
