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Establishment of three bleomycin‐resistant human carcinoma cell lines and their cross‐resistance to other antitumor agents
Author(s) -
Urade Masahiro,
Sugi Masakazu,
Miyazaki Tadashi
Publication year - 1988
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(19880415)61:8<1501::aid-cncr2820610805>3.0.co;2-4
Subject(s) - bleomycin , hela , cell culture , incubation , microbiology and biotechnology , in vitro , cross resistance , biology , medicine , chemotherapy , biochemistry , genetics
Three bleomycin‐resistant (BLMr) human carcinoma cell lines (HeLa‐BLMr, KB‐BLMr, and Hepd‐uvBLMr) were established in culture by progressively increasing the concentration of bleomycin (BLM). HeLa‐BLMr and KB‐BLMr were obtained after 5 and 2 months of incubation with BLM, whereas the establishment of Hepd‐uvBLMr required 3 months of incubation with BLM after ultraviolet treatment. These cells have been successfully subcultured for more than 150 passages during more than 2 years in the presence of 1 μg/ml of BLM. The degrees of BLM resistance were 20‐fold, 11.6‐fold, and 186‐fold for HeLa‐BLMr, KB‐BLMr, and Hepd‐uvBLMr, respectively, and the resistant phenotype of both HeLa‐BLMr and Hepd‐uvBLMr was stable when they were cultured for 30 passages in BLM‐free medium, but unstable in KB‐BLMr. Although each cell line exhibited cross‐resistance to 3 to 5 other antitumor agents including peplomycin, combined use of BLM with a polyene antibiotic, a calcium channel blocker, or a poly(ADP‐ribose) polymerase inhibitor overcame the BLM resistance in vitro to various degrees.