Effects of suramin, a polyanionic drug inducing lysosomal storage disorders on tooth germs in vitro.
Suramin, a potent inhibitor of lysosomal enzymes, is commonly employed as a tool for inducing experimental mucopolysaccharidosis and lipidosis. The effects of the drug on embryonic mouse molars were analysed. Presecretory ameloblasts and odontoblasts were loaded with lysosome-like vacuoles. Staining with MC22-33F, an antibody to choline phospholipids and sphingomyelin, was completely reversed in the suramin-treated germs, in that it stained only presecretory ameloblasts (versus odontoblasts and some pulpal cells in the control group), according to a developmentally regulated pattern. The suramin-induced cytoplasmic changes were reminiscent of the features of mucopolysaccharidoses and lipidoses. The basement membrane, separating the enamel organ from the dental papilla, displayed suramin-induced patches, and in predentin collagen fibrillogenesis was found to be disturbed. Furthermore, autoradiography was employed to reveal uptake and distribution of [3H] suramin in the cells and predentin. Finally, a suramin-induced disturbance of the metabolism of sulphated macromolecules was found. The results imply that suramin effects in vitro on tooth germs can be used as a useful experimental model with to study both the action of the drug as well as cell and extracellular matrix perturbations in a mucopolysaccharidosis-like condition.
Laboratoire de Biologie et Biomatériaux du Milieu Buccal et Osseux, Faculté de Chirurgie Dentaire LA 1505, Montrouge, France.
A
A
Gritli-Linde
J V
JV
Ruch
M P
MP
Mark
S
S
Lécolle
M
M
Goldberg
D000818:Animals; D001345:Autoradiography; D001485:Basement Membrane; D003094:Collagen / Q000096:biosynthesis; D005260:Female; D005455:Fluorescent Antibody Technique; D016464:Lysosomal Storage Diseases / Q000139:chemically induced / Q000378:metabolism; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D008854:Microscopy, Electron; D009924:Organ Culture Techniques; D010743:Phospholipids / Q000032:analysis; D011247:Pregnancy; D013109:Sphingomyelins / Q000032:analysis; D013498:Suramin / Q000494:pharmacology*; D014083:Tooth Germ / Q000196:embryology* / Q000378:metabolism* / Q000648:ultrastructure
D010743:Phospholipids; D013109:Sphingomyelins; D013498:Suramin; D003094:Collagen