Effect of bleomycin, neocarzinostatin, and hydroxyurea on the preformed carrageenin granuloma in rats: mechanism of hyaluronic acid accumulation by bleomycin.

In order to elucidate whether the effects of bleomycin on the production or accumulation of intercellular substances by rat carrageenin granuloma are specific to bleomycin or a general response of the granulomatous tissue to the substances interfering with DNA synthesis, we examined the wet (or dry) weight and various components (DNA and glycosaminoglycans) in the granulomatous tissue of rats treated with bleomycin, neocarzinostatin, or hydroxyurea. The changes in various parameters of the granuloma after withdrawal of the inhibitors of DNA synthesis were different with different inhibitors tested. The highest recovery rate of DNA contents in the granulomatous tissue observed after withdrawal of bleomycin. It was also found that bleomycin caused much higher accumulation of hyaluronic acid in rat carrageenin granuloma than neocarzinostatin or hydroxyurea. This accumulation mechanism was indicated to be the results of the inhibition of mucopolysaccharidase activities via cells rather than those of the stimulation of glycosaminoglycan synthesis. These findings obtained in our experimental granuloma-system are of particular importance in considering the mechanism of the side effects of bleomycin.