BCNU-induced increase in sulfated glycosaminoglycan production by human bone marrow stromal cells.
The etiology of alkylator-induced leukemia is obscure, but may be due in part to alternations in the bone marrow stromal microenvironment. Marrow extracellular matrix, including collagen, glycosaminoglycans/proteoglycans, and glycoproteins, may play a crucial role in the control of normal and abnormal hematopoiesis. Twenty-four hours after seeding, confluent human bone marrow stromal cell cultures were exposed for 3 h to 15 micrograms/ml of 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU), an alkylating agent with leukemogenic potential. On the eighth day of culture, [35S]sulfate was added and radiolabeled glycosaminoglycan(s) (GAGs) was harvested 24 h later. BCNU treatment resulted in a 104% increase of the radiolabel incorporation into cetylpyridinium chloride precipitable GAG. In addition, spectrophotometric measurement of total GAG in treated cells revealed a similar GAG increase. However, BCNU treatment did not alter compartmental GAG distribution or GAG species. Our results demonstrate a profound quantitative change in the production of important extracellular matrix components by bone marrow stromal cells after exposure to a nitrosourea. This increase may be a factor in microenvironmental alterations leading to bone marrow toxicity following alkylator exposure.
D001853:Bone Marrow / Q000187:drug effects* / Q000378:metabolism; D001854:Bone Marrow Cells; D002330:Carmustine / Q000494:pharmacology*; D002478:Cells, Cultured; D002809:Chondroitin Sulfates / Q000096:biosynthesis; D003871:Dermatan Sulfate / Q000096:biosynthesis; D005109:Extracellular Matrix / Q000378:metabolism; D006025:Glycosaminoglycans / Q000096:biosynthesis*; D006497:Heparan Sulfate / Q000096:biosynthesis; D006801:Humans; D013268:Stimulation, Chemical
D002330:Carmustine; D002809:Chondroitin Sulfates; D003871:Dermatan Sulfate; D006025:Glycosaminoglycans; D006497:Heparan Sulfate