[Sensitivity to bleomycin of human cultured tumor cells and analysis of related factors].
Several types of human cultured tumor cells were tested for the sensitivity to BLM, an effective antitumor antibiotic for epidermoid (squamous cell) carcinomas. Three cell lines (HeLa, KB, Hepd) derived from epidermoid carcinomas were very sensitive to BLM under concentrations tested, whereas BLM-resistant HeLa cells (HeLa-BLMr), neoplastic cells derived from salivary glands (HPA, HSG), malignant fibrous histiocytoma (MFH) and melanoma (MEC) were much less sensitive to BLM than epidermoid carcinoma cell lines under the same conditions. To investigate the possible mechanism of BLM resistance, these cell lines, namely HeLa, HeLa-BLMr, HSG and MEC, were examined for i) BLM permeability into cells by using 3H-PEP which was a new derivative of BLM, ii) BLM-inactivating activity in cell extracts by bioassay for antibacterial activity with B. subtilis PCI 219 strain, and iii) DNA repair activity after UV irradiation. Consequently, as compared with BLM-sensitive HeLa cells, BLM less sensitive HeLa-BLMr, HSG and MEC cells showed 34%, 50% and 39% reduction per 10(6) cells in BLM permeability, 1.6-, 5.6- and 4.7-fold increase per mg protein in BLM inactivating activity, and 24.5-, one and 8-fold enhancement in DNA repair activity, respectively. Therefore, it was indicated that above three factors at least were involved in the BLM sensitivity of human tumor cells.
D001761:Bleomycin / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D004260:DNA Repair / Q000187:drug effects; D004351:Drug Resistance; D006367:HeLa Cells; D006801:Humans
D001761:Bleomycin