Stimulatory effect of bleomycin on the hyaluronic acid synthetase in cultured fibroblasts

Abstract

The mechanism of the stimulatory effect of bleomycin on the production of hexosamine-containing substances by cultured fibroblasts was studied by measuring changes in the activity of hyaluronic acid (HA) synthetase. HA synthetase activity was increased by 1 gmg bleomycin/ml, and its stimulatory effect could be detected 4 days after the start of bleomycin treatment and was enhanced by lenthening the time of treatment, i.e. by 96 per cent for an 8-day treatment. In cell-free systems, however, bleomycin showed no stimulatory effect on this enzyme activity. The enhancement of HA synthetase activity by bleomycin was inhibited by the addition of cycloheximide or actinomycin D. The synthesis of HA was much less influenced by cycloheximide than was that og glycoprotein and sulfated glycosaminoglycan. From our results it can be concluded that HA synthetase activity, induced when the old medium of stationary cultures was renewed with fresh medium containing 5% fetal bovine serum, was significantly enhanced by the addition of bleomycin. However, the detailed mechanism of enhancement of HA synthetase activity has not yet been elucidated.