scholarly journals Gene amplification-associated cytogenetic aberrations and protein changes in vincristine-resistant Chinese hamster, mouse, and human cells.

1985 ◽  
Vol 100 (2) ◽  
pp. 588-597 ◽  
Author(s):  
M B Meyers ◽  
B A Spengler ◽  
T D Chang ◽  
P W Melera ◽  
J L Biedler
Keyword(s):  
Gene Amplification ◽  
Vinca Alkaloid ◽  
Chinese Hamster ◽  
Selection Procedure ◽  
Cross Resistance ◽  
Chinese Hamster Cells ◽  
Development Of Resistance ◽  
Cytogenetic Aberrations ◽  
Medium Level ◽  
Resistant Cells

We carried out cytogenetic studies of four Chinese hamster, mouse, and human cell lines selected for high levels of resistance (500- to 4,000-fold) to vincristine (VCR) by a multistep selection procedure. All cells examined contained gene amplification-associated metaphase chromosome abnormalities, either homogeneously staining regions (HSRs), abnormally banding regions (ABRs), or double-minute chromosomes (DMs); control actinomycin D- and daunorubicin-resistant hamster lines did not exhibit this type of chromosomal abnormality. VCR-resistant Chinese hamster sublines exhibited both increased synthesis of the protein V19 (Mr 19,000; pl = 5.7) and increased concentrations of V19 polysomal mRNA. When VCR-resistant cells were grown in drug-free medium, level of resistance, synthesis of V19, and amount of V19 mRNA declined in parallel with mean length of the HSR or mean number of DMs per cell. Cross-resistance studies indicate that VCR-resistant cells have increased resistance both to antimitotic agents and to a wide variety of agents unrelated to VCR in chemical structure and/or mechanism of action. Our studies of tubulin synthesis in Chinese hamster cells indicate no overproduction of tubulin or presence of a mutant tubulin species. Comparison with antifolate-resistant Chinese hamster cells known to contain amplified dihydrofolate reductase genes localized to HSRs or ABRs strongly suggests that the HSRs, ABRs, or DMs of the Vinca alkaloid-resistant sublines likewise represent cytological manifestations of specifically amplified genes, possibly encoding V19, involved in development of resistance to VCR.

Gene amplification in V79 Chinese hamster cells

1987 ◽  
Vol 181 (2) ◽  
pp. 345
Author(s):  
L. Ottaggio ◽  
S. Bonatti ◽  
F. Tosetti ◽  
M. Miele ◽  
P. Degan ◽  
...  
Keyword(s):  
Gene Amplification ◽  
Chinese Hamster ◽  
Chinese Hamster Cells

Induction of CAD gene amplification by restriction endonucleases in V79,B7 Chinese hamster cells

1989 ◽  
Vol 225 (1-2) ◽  
pp. 61-64 ◽  
Author(s):  
P. Cavolina ◽  
C. Agnese ◽  
A. Maddalena ◽  
G. Sciandrello ◽  
A. Di Leonardo
Keyword(s):  
Gene Amplification ◽  
Chinese Hamster ◽  
Restriction Endonucleases ◽  
Chinese Hamster Cells ◽  
Cad Gene

scholarly journals V79 Chinese-hamster cells rendered resistant to high cadmium concentration also become resistant to oxidative stress

1988 ◽  
Vol 256 (2) ◽  
pp. 475-479 ◽  
Author(s):  
A C Mello-Filho ◽  
L S Chubatsu ◽  
R Meneghini
Keyword(s):  
Oxidative Stress ◽  
Xanthine Oxidase ◽  
Superoxide Anion ◽  
Cadmium Concentration ◽  
Antioxidant Properties ◽  
Chinese Hamster ◽  
Chinese Hamster Cells ◽  
Cell Basis ◽  
High Concentrations ◽  
Resistant Cells

Chinese hamster cells (V79) resistant to high concentrations of Cd2+ in the medium were obtained by using the procedure of Beach & Palmiter [(1981) Proc. Natl. Acad. Sci. U.S.A. 78, 2110-2114], which in mouse led to amplification of metallothionein (MT) genes and to an enrichment in cellular MT. The Cd-resistant V79 clones isolated were significantly more resistant than parental cells to oxidative stress by extracellular H2O2 or a mixture of H2O2 and superoxide anion (O2-) generated by xanthine oxidase plus acetaldehyde. On a per-cell basis, there was no difference between the two cells in their total H2O2-decomposing or O2-(-)dismutating activity. The most likely explanation is that an enrichment in MT content in the Cd-resistant cells was responsible for this effect, because of the antioxidant properties already described for this protein.

Inhibition of initiator-induced SV40 gene amplification in SV40-transformed Chinese hamster cells by infection with a defective parvovirus

1983 ◽  
Vol 32 (5) ◽  
pp. 591-595 ◽  
Author(s):  
Jörg R. Schlehofer ◽  
Regine Heilbronn ◽  
Brigitte Georg-Fries ◽  
Harald Zur Hausen
Keyword(s):  
Gene Amplification ◽  
Chinese Hamster ◽  
Chinese Hamster Cells

Gene amplification and gene deletion are induced at different rates in V79/AP4 Chinese hamster cells

Mutagenesis ◽  
1993 ◽  
Vol 8 (5) ◽  
pp. 411-415
Author(s):  
Lucia Vatteroni ◽  
Antonio Piras ◽  
Arcangela Moretti ◽  
Giuseppe Rainaldi
Keyword(s):  
Gene Amplification ◽  
Gene Deletion ◽  
Chinese Hamster ◽  
Chinese Hamster Cells

scholarly journals Cytogenetic manifestations associated with the reversion, by gene amplification, at the HGPRT locus in V79 Chinese hamster cells

1989 ◽  
Vol 53 (3) ◽  
pp. 201-206
Author(s):  
A. Di Leonardo ◽  
C. Agnese ◽  
P. Cavolina ◽  
A. Maddalena ◽  
G. Sciandrello ◽  
...  
Keyword(s):  
Gene Amplification ◽  
Cytogenetic Analysis ◽  
Blot Hybridization ◽  
Chinese Hamster ◽  
Mutant Line ◽  
Dot Blot ◽  
Chinese Hamster Cells ◽  
Dot Blot Hybridization ◽  
Clonal Origin

SummarySome HGPRT spontaneous revertants were isolated from a mutant line (E2) of V79 Chinese hamster cells and phenotypically characterized. Dot–Blot hybridization with a 32P-Iabelled HGPRT probe revealed an increase in the number of HGPRT sequences in some of these revertants, suggesting the occurrence of gene amplification. Cytogenetic analysis performed in three of these revertants showed a characteristic abnormally banding region (ABR) on the elongated p arm of the X chromosome. In Situ hybridization in one revertant (RHE2) showed that the amplified sequences reside on the p+ arm of the X chromsome in two different localizations. Because of the very probable clonal origin of the revertant, these features indicate that the amplified sequences might rearrange after their integration into the chromosome.

scholarly journals SOME BIOCHEMICAL PROPERTIES OF CHINESE HAMSTER CELLS SENSITIVE AND RESISTANT TO ACTINOMYCIN D

1974 ◽  
Vol 63 (3) ◽  
pp. 773-779 ◽  
Author(s):  
Robert H. F. Peterson ◽  
Judith A. O'Neil ◽  
June L. Biedler
Keyword(s):  
Rna Synthesis ◽  
Actinomycin D ◽  
Chinese Hamster ◽  
Biochemical Properties ◽  
Metabolic Inhibitors ◽  
Drug Resistant ◽  
Temperature Dependent ◽  
Chinese Hamster Cells ◽  
Uptake And Release ◽  
Resistant Cells

A graded series of drug-resistant Chinese hamster sublines has been examined for biochemical changes accompanying resistance to actinomycin D. The most highly resistant subline, DC-3F/AD X, is maintained at 10 µg/ml of the antibiotic. It was shown that over 250 times more actinomycin D is required to inhibit RNA synthesis in this subline than in the parental DC-3F line. The DC-3F/AD X subline was also shown to have a somewhat reduced capacity to transport uridine as compared to parental cells. Sensitive cells took up over 50 times more tritiated antibiotic than the most resistant cells, as determined in a 1-h assay. Uptake of actinomycin D was shown to be temperature-dependent in both resistant and sensitive cells and was not influenced by various metabolic inhibitors. Resistance could not be explained by a rapid uptake and release of the antibiotic, as demonstrated in efflux experiments, or by its metabolism. In addition, highly resistant cells which are cross-resistant to puromycin were shown to have a reduced capacity to take up labeled puromycin. These studies provide further evidence indicating that the mechanism of resistance to actinomycin D is reduced permeability to drug and suggesting that cell membrane alteration accounts for resistance to both actinomycin D and puromycin.

Gene amplification as a mechanism of reversion at the HPRT locus in V79 chinese hamster cells

1984 ◽  
Vol 119 (3) ◽  
pp. 341-348 ◽  
Author(s):  
Olga Zownir ◽  
James C. Fuscoe ◽  
Raymond Fenwick ◽  
John Morrow
Keyword(s):  
Gene Amplification ◽  
Chinese Hamster ◽  
Chinese Hamster Cells ◽  
Hprt Locus

scholarly journals Resistance to Cytarabine in Mantle Cell Lymphoma Is Mediated By Down-Regulation of Deoxycytidine Kinase at the Protein Level

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1769-1769 ◽  
Author(s):  
Catja Freiburghaus ◽  
Venera Kuci Emruli ◽  
Angelica Johansson ◽  
Roger Olsson ◽  
Fredrik Ek ◽  
...  
Keyword(s):  
Research Funding ◽  
Cell Lymphoma ◽  
Cross Resistance ◽  
Deoxycytidine Kinase ◽  
High Dose ◽  
Down Regulation ◽  
Development Of Resistance ◽  
Mantle Cell ◽  
High Dose Cytarabine ◽  
Resistant Cells

Abstract INTRODUCTION: The addition of high-dose cytarabine to mantle cell lymphoma (MCL) treatment regimens has significantly prolonged survival of patient subgroups, but relapses are common and are usually associated with treatment resistance. High-dose cytarabine is effective due to the improved retention of ara-CTP by target cells, but likewise toxic, causing mainly hematological side effects. Thus, understanding the molecular mechanism(s) responsible for resistance and to identify predictive markers for resistance and/or sensitizing agents would be of great clinical value. In an attempt to elucidate those mechanisms and to create a tool for drug discovery investigations, we established a unique and molecularly reproducible cytarabine resistant model from the Z138 MCL cell line. Using molecular profiling, we confirm that down-regulation of the deoxycytidine kinase (dCK) protein is key to development of resistance. The MCL resistance model was carefully characterized by screening with annotated compound libraries focused on (i) chemotherapeutics to identify potential cross-resistance and/or sensitivity, and (ii) epigenetic pathways to investigate sensitivity, but also to select individual candidates for sensitization of cytarabine resistant cells. Furthermore, we investigated the hypothesis that the levels of dCK at diagnosis can be used to predict cytarabine resistance through measurement of event-free survival using the Nordic MCL 2/3 cohort, where patients are treated with a combinatorial protocol including high-dose cytarabine. MATERIAL AND METHODS: The first resistant sub-clone defined as Z138 Cytarabine Resistant (Z138-CytR) was established by continuous exposure of wild type Z138 Cytarabine Naïve Sensitive cells (Z138-CytNS) to increasing concentrations (0.005 - 0.3 µM) of cytarabine. Using this model, we could identify the approximate time to resistance development, and utilize this information for developing a novel highly reproducible time-controlled cytarabine resistant model. Molecular changes were investigated by protein and gene expression analyses. Utilizing drug libraries, the cell model was further used to identify substances with growth reducing effect on cytarabine resistant cells. RESULTS AND CONCLUSION: Gene expression profiling revealed that major transcriptional changes occur during the initial phase of adaptation to cellular growth in cytarabine containing media, and only few genes are deregulated upon development of resistance. Instead, resistance to cytarabine was shown to be mediated by down-regulation of the dCK protein, responsible for activation of nucleoside analogue prodrugs. Consequently, cytarabine resistant cells showed cross-resistance to other nucleoside analogues including gemcitabine, cladribine and fludarabine. Of major importance, using drug libraries, we identify substances with growth reducing effect on cytarabine resistant cells. Further investigations are needed to pinpoint compounds that can prevent the down-regulation, or possibly restore dCK protein levels. The possibility to predict cytarabine resistance in diagnostic samples was assessed, but analysis show that the majority of patients have moderate to high expression of dCK at diagnosis, corresponding well to the initial successful response to cytarabine-containing treatment protocols. Disclosures Geisler: Roche: Consultancy; Janssen: Consultancy; Celgene: Consultancy; Sanofi: Consultancy. Jerkeman:Celgene: Research Funding; Gilead: Research Funding; Janssen: Research Funding; Amgen: Research Funding; Mundipharma: Research Funding.

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