Open AccessAcute Metabolic Effects of Nitrogen Mustard and Thiotepa on Rabbit Articular Cartilage and Synovium
Author(s) -
Mankin Henry J.,
Lippiello Louis
Publication year - 1979
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.1780220604
Subject(s) - thiotepa , nitrogen mustard , cartilage , in vivo , chemistry , glycosaminoglycan , pharmacology , biochemistry , medicine , anatomy , biology , cyclophosphamide , microbiology and biotechnology , chemotherapy
Metabolic alterations in immature rabbit joint tissues 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 had 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 35 S‐Thiotepa. Furthermore, trypsin significantly reduced labeling of cartilage with 14 C‐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 time of exposure to the agents and the relative DNA‐RNA synthetic activity of the joint tissue.