Ultrastructural changes accompany inhibition of proteoglycan synthesis in chondrocytes by Cyclofenil diphenol.
Cyclofenil diphenol, a weak non-steroidal oestrogen, profoundly inhibits [35S]proteoglycan synthesis in cultures of Swarm chondrosarcoma chondrocytes under conditions in which protein synthesis is only marginally reduced. In the present experiments it was shown that after a 40-min treatment with Cyclofenil diphenol (90 micrograms ml-1) most of the normally abundant Golgi stacks in these cells disappeared and after 60 min they were absent. After 2-3 h treatment the cisternae of the endoplasmic reticulum (ER) were grossly distended and transformed into large ribosome-studded vesicles containing flocculent and filamentous material. These changes were dependent on the concentration of Cyclofenil and were fully reversible within 21 h of withdrawing the drug. The ultrastructural changes differed in some aspects if protein synthesis was blocked with cycloheximide for 15 min or 180 min before and during treatment with Cyclofenil. The Golgi disappeared but the ER cisternae, though distended, formed a continuous network and swollen ribosome-studded vesicles did not develop. However, non-membrane-bounded structures containing lipid droplets and material of low electron density developed in the cytoplasm under these conditions. The ultrastructural changes induced by Cyclofenil differ from those induced by monensin and diethylcarbamazine, suggesting that the drug acts at a different point in the secretory pathway for macromolecules.
Department of Biochemistry, Charing Cross and Westminster Medical School, London, UK.
C A
CA
Lancaster
P R
PR
Fryer
S
S
Griffiths
R M
RM
Mason
D000818:Animals; D002356:Cartilage / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D003408:Cresols / Q000494:pharmacology*; D003506:Cyclofenil / Q000494:pharmacology*; D008854:Microscopy, Electron; D011509:Proteoglycans / Q000096:biosynthesis*; D051381:Rats
D003408:Cresols; D011509:Proteoglycans; D003506:Cyclofenil