Stimulatory effect of bleomycin on the synthesis of acidic glycosaminoglycans in cultured fibroblasts derived from rat carrageenin granuloma.

Cultured fibroblasts derived from rat carrageenin granuloma were treated with bleomycin and the synthesis of hexosamine-containing substances was compared with that in control cells. Four day treatment with o.1 mug bleomycin/ml resulted in a significant increase of the production of these macromolecules by the cells, though DNA synthesis was remarkably inhibited at this dose of bleomycin. The stimulatory effect could be seen as early as the second day of bleomycin treatment, and was enhanced with increasing treatment time. Further fractionation of the hexosamine-containing substances revealed that synthesis of acidic glycosaminoglycans was more sensitive to bleomycin than that of glycoproteins, i.e., acidic glycosaminoglycans increased by 80% and glycoproteins by 53% after four day treatment with 0.1 mug bleomycin/ml. The increased components of acidic glycosaminoglycans included not only hyaluronic acid but also sulphated glycosaminoglycans. Collagen synthesis was increased by 23% by the same dose of bleomycin. N-Acetyl-beta-glucosaminidase, one of the degradation enzymes for acidic glycosaminoglycans released into the cultured medium, was decreased significantly by bleomycin.