A new human breast carcinoma cell line resistant to DNA-damaging drugs.
To investigate the phenomenon of active dissociation of the vital dye, Hoechst 33342 (Ho342), from DNA (DNA clearing), a new MCF7HoeR-7 human breast carcinoma cell line was isolated from parent MCF7 cells by step-wise selection with increasing concentrations of Ho342. This cell line possesses an enhanced ability for DNA clearing. The MCF7HoeR-7 line is characterised in detail and compared with the parental MCF7 line and a typical P-glycoprotein-mediated multidrug resistant (MDR) cell line, MCF7/Adr. MCF7HoeR-7 cells have an increased population growth rate, a lower DNA content and a reduced number of chromosomes. Enhanced DNA clearing in MCF7HoeR-7 cells is associated with the high resistance of the cells to the toxic effects of Ho342 and cross-resistance to etoposide, a topoisomerase II inhibitor in clinical use. The MCF7HoeR-7 and parent MCF7 cell lines have similar expression levels of transport proteins. The results obtained confirm that DNA clearing is an atypical MDR mechanism in tumour cells.
Levina
Vera V
VV
Petersburg Nuclear Physics Institute, Russian Academy of Science, Gatchina, Russian Federation. veralevina@mail.ru
Drobchenko
Eugeny A
EA
Shabalina
Elena V
EV
D001562:Benzimidazoles / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D001943:Breast Neoplasms / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000008:administration & dosage / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D001562:Benzimidazoles; D005047:Etoposide; D004247:DNA; C017807:bisbenzimide ethoxide trihydrochloride