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

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.

Author(s):  
Awtar Krishan ◽  
Dora Hsu

Cells exposed to antitumor plant alkaloids, vinblastine and vincristine sulfate have large proteinacious crystals and complexes of ribosomes, helical polyribosomes and electron-dense granular material (ribosomal complexes) in their cytoplasm, Binding of H3-colchicine by the in vivo crystals shows that they contain microtubular proteins. Association of ribosomal complexes with the crystals suggests that these structures may be interrelated.In the present study cultured human leukemic lymphoblasts (CCRF-CEM), were incubated with protein and RNA-synthesis inhibitors, p. fluorophenylalanine, puromycin, cycloheximide or actinomycin-D before the addition of crystal-inducing doses of vinblastine to the culture medium. None of these compounds could completely prevent the formation of the ribosomal complexes or the crystals. However, in cells pre-incubated with puromycin, cycloheximide, or actinomycin-D, a reduction in the number and size of the ribosomal complexes was seen. Large helical polyribosomes were absent in the ribosomal complexes of cells treated with puromycin, while in cells exposed to cycloheximide, there was an apparent reduction in the number of ribosomes associated with the ribosomal complexes (Fig. 2).


1988 ◽  
Vol 256 (2) ◽  
pp. 475-479 ◽  
Author(s):  
A C Mello-Filho ◽  
L S Chubatsu ◽  
R Meneghini

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.


1979 ◽  
Vol 183 (1) ◽  
pp. 179-180 ◽  
Author(s):  
Y M Heimer ◽  
E Riklis

Trioxalen (trimethylpsoralen) plus near-u.v. light, a potent inhibitor of DNA and RNA synthesis, inhibits the induction of ornithine decarboxylase in stationary-phase V79 fibroblasts. It does not affect the translation of pre-existing mRNA. The method, in view of its high degree of specificity and precise timing, is a better choice for inhibiting RNA synthesis than the commonly used chemical inhibitors and precursor analogues.


1969 ◽  
Vol 42 (2) ◽  
pp. 366-376 ◽  
Author(s):  
M. M. Elkind ◽  
E. Kano ◽  
H. Sutton-Gilbert

Using Chinese hamster cells in culture, we have measured the effectiveness of actinomycin D to suppress division as a function of the position, or age, of a cell in its growth cycle. Cells were first exposed to millimolar concentrations of hydroxyurea in order to produce a synchronized population just before the onset of DNA synthesis. Thereafter, the survival response after 30 min exposures to actinomycin D was measured. Cells become resistant as they enter the S phase and then sensitive again in the latter part of S. When they reach G2 (or G2-mitosis) they are maximally resistant; at 1.0 µg/ml, for example, the survival in G2 is 30-fold greater than it is in G1. These results, plus measurements reported earlier on the interaction of damage in S cells due to actinomycin D and X-irradiation, suggest that the age-response pattern of the toxic effects of this drug probably reflects both the functional capacity of DNA-actinomycin complexes and the ability of this antibiotic to penetrate chromatin and bind to DNA.


1976 ◽  
Vol 14 (1-2) ◽  
pp. 57-65 ◽  
Author(s):  
Fabrizio Palitti ◽  
Ruggero Ricordy ◽  
Paolo Perticone ◽  
Silvana D'andrea ◽  
Marco Rizzoni

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