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Author Zhan, Q.; Fan, S.; Bae, I.; Guillouf, C.; Liebermann, D.A.; O'Connor, P.M.; Fornace, A.J.J. file  url
Title Induction of bax by genotoxic stress in human cells correlates with normal p53 status and apoptosis Type Journal Article
Year 1994 Publication Oncogene Abbreviated Journal Oncogene  
Volume 9 Issue 12 Pages 3743-3751  
Keywords Apoptosis/*genetics; Gene Expression Regulation/*drug effects/genetics/radiation effects; *Genes, p53; Humans; Mutagens/*toxicity; Neoplasms/genetics; Proto-Oncogene Proteins/*genetics; Proto-Oncogene Proteins c-bcl-2; Tumor Cells, Cultured; bcl-2-Associated X Protein  
Abstract DNA-damaging agents such as ionizing radiation (IR) activate the tumor suppressor p53 and in some cases can cause apoptosis. M1 cells, which do not express the endogenous tumor suppressor gene p53, undergo apoptosis following activation of a temperature sensitive p53 transgene, where it has been shown that bax, an important mediator of apoptosis, is a p53 target gene (Selvakumaran et al, Oncogene 9, 1791-8, 1994). Since p53 can function as a transcription factor after activation by IR, the genetic response to this stress was examined in a panel of human cells with defined p53 status. Like the p53-regulated gene gadd45, bax was rapidly induced, as measured by increased mRNA levels, in the p53 wt (wild type) human myeloid line ML-1, and it was not induced in cells lacking functional p53. However, unlike other p53-regulated genes, bax was only induced in p53 wt cells in which IR also triggered apoptosis. In the case of bcl2, which opposes bax function, mRNA levels were reduced in ML-1 cells after IR. Thus, bax appears to be an unique p53-regulated gene in that its induction by IR not only requires functional p53 but also requires that the cells be apoptosis “proficient.”  
Call Number Serial 2172  
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Author Jakubikova, J.; Duraj, J.; Hunakova, L.; Chorvath, B.; Sedlak, J. file  url
Title PK11195, an isoquinoline carboxamide ligand of the mitochondrial benzodiazepine receptor, increased drug uptake and facilitated drug-induced apoptosis in human multidrug-resistant leukemia cells in vitro Type Journal Article
Year 2002 Publication Neoplasma Abbreviated Journal Neoplasma  
Volume 49 Issue 4 Pages 231-236  
Keywords Antineoplastic Agents/*metabolism/*pharmacology/toxicity; Apoptosis/*drug effects; Biological Transport; Carcinoma/drug therapy/metabolism; Daunorubicin/*metabolism/toxicity; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Drug Synergism; Female; Fluoresceins/metabolism; Fluorescent Dyes/metabolism; HL-60 Cells; Humans; Isoquinolines/metabolism/*pharmacology; Leukemia, Myeloid/*drug therapy/metabolism; Ligands; Mitochondrial Proteins/metabolism; Ovarian Neoplasms/drug therapy/metabolism; P-Glycoprotein/genetics; Receptors, GABA-A/metabolism; Tumor Cells, Cultured  
Abstract The isoquinoline peripheral benzodiazepine receptor ligand PK11195 increased drug (daunomycin)- and fluorochrome (calcein-AM) uptake and induced apoptosis detected by flow cytometry (FCM) technique, DNA electrophoretic analysis and poly(ADP-ribose) polymerase (PARP) cleavage in human multidrug-resistant myeloid leukemia (BL-60/VCR) and ovarian carcinoma (A2780/ADR) cells in vitro. The position of PK11195 with respect to drug-resistance modulator (DRM) efficiency, compared to the reference DRMs with the aid of FCM technique, was as follows: PSC833 > verapamil > PK11195 > vincristine. Our data show up to now not indicated observation that PK11195 possesses multidrug resistance modulating activity.  
Call Number Serial 398  
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