Differential cytotoxicity of anticancer agents in pre- and post-immortal lymphoblastoid cell lines.
We studied the cytotoxic effect of various anticancer agents on lymphoblastoid cell lines transformed by Epstein-Barr virus. Post-immortal N0005 (post-N0005) is an immortalized cell line derived from pre-immortal N0005 (pre-N0005) accompanied by increased telomerase activity, short-telomere, abnormal karyotypes, mutation of p53 gene, down regulation of p16/Rb and the ability to grow in soft agar medium. Compared with pre-N0005 cells, post-N0005 cells were significantly (p<0.001 by the Student t test) more resistant to the killing activity of seven DNA-modifying agents: camptothecin, etoposide, bleomycin, fluorouracil, thioguanine, melphalan and actinomycin D. However, both pre-N0005 and post-N0005 cells showed similar levels of cytotoxicity against four DNA-non-modifying agents: colchicine, paclitaxel, vincristine and methotrexate. DNA-modifying and DNA-non-modifying agents are distinguished by their different sensitivities with pre-N0005 and post-N0005. Based on these results, we propose that pre-N0005 and post-N0005 cell lines be used as a new method to assess and screen anticancer agents.
Sawada
Kaori
K
GeneCare Research Institute, Kanagawa, Japan.
Noda
Keisuke
K
Nakajima
Hiroto
H
Shimbara
Naoki
N
Furuichi
Yasuhiro
Y
Sugimoto
Masanobu
M
D000970:Antineoplastic Agents / Q000633:toxicity*; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry; D004854:Herpesvirus 4, Human / Q000502:physiology; D006801:Humans
D000970:Antineoplastic Agents