Internalisation of the bleomycin molecules responsible for bleomycin toxicity: a receptor-mediated endocytosis mechanism.

摘要: Bleomycin (BLM) does not diffuse through the plasma membrane but nevertheless displays cytotoxic activity due to DNA break generation. The aim of study was describe mechanism BLM internalisation. We previously provided evidence for existence BLM-binding sites at surface DC-3F Chinese hamster fibroblasts, as well their involvement in cytotoxicity on cells and related BLM-resistant sublines. Here we report that A253 human subline C-10E also possessed a protein ca. 250 kDa specifically binding BLM. Part this cell resistance could be explained by decrease number exposed with respect cells. comparison between exposing similar revealed faster fluid phase endocytosis, greater sensitivity Moreover, experimental modification endocytotic vesicle size showed directly correlated flux area engulfed during endocytosis rather than volume incorporated. Thus, would internalised receptor-mediated which first require its receptor then transfer complex into intracellular vesicles, followed entry cytosol, probably from nonacidic compartment.