Unbalanced growth and cell death in HeLa S3 cultures treated with DNA synthesis inhibitors

1981 ◽  
Vol 107 (1) ◽  
pp. 115-122 ◽  
Author(s):  
Oskar S. Frankfurt
Keyword(s):  
Cell Death ◽  
Dna Synthesis ◽  
Unbalanced Growth ◽  
Hela S3 ◽  
Dna Synthesis Inhibitors

HYPERTROPHY AND HYPERPLASIA IN THE MOUSE UTERUS AFTER OESTROGEN TREATMENT: AN AUTORADIOGRAPHIC STUDY

1973 ◽  
Vol 56 (1) ◽  
pp. 133-NP ◽  
Author(s):  
L. MARTIN ◽  
C. A. FINN ◽  
GAIL TRINDER
Keyword(s):  
Cell Death ◽  
Dna Synthesis ◽  
Proliferative Response ◽  
Autoradiographic Study ◽  
Luminal Epithelium ◽  
Uterine Tissue ◽  
Mouse Uterus ◽  
Oestrogen Treatment ◽  
Ovariectomized Mice

SUMMARY The uteri of untreated ovariectomized mice consisted almost entirely of myometrium and connective tissue stroma. After oestrogenic stimulation these tissues underwent marked hypertrophy, but showed little proliferation. The luminal epithelium underwent marked hyperplasia, with most cells dividing twice to quadruple cell numbers by 35–40 h, when they made up 10–12% of the uterine tissue volume and 20% of the total uterine cell population. The proliferative response was rapid, highly synchronized and short-lived. The number of cells incorporating [3H]thymidine first increased 8·5 h after oestradiol-17β and by 13–16 h 60–70% were engaged in DNA synthesis. Up to 21 h cell-death was minimal. From 21 h onwards the proliferation rate declined and the rate of cell death increased. A second injection of oestrogen prevented the rise in death rate and produced a second smaller burst of DNA synthesis. Cells in DNA synthesis or mitosis were insensitive to oestrogen. A smaller proliferative response occurred in the glands: only 25% of cells entered DNA synthesis after the first injection of oestradiol and none after the second. Gland cells appeared to die in situ and there was no evidence that they migrated into the luminal epithelium.

scholarly journals Modification of X-Ray-Induced Killing of HeLa S3 Cells by Inhibitors of DNA Synthesis

1967 ◽  
Vol 7 (6) ◽  
pp. 779-795 ◽  
Author(s):  
Barbara G. Weiss ◽  
L.J. Tolmach
Keyword(s):  
Dna Synthesis ◽  
X Ray ◽  
Hela S3 ◽  
Hela S3 Cells

Targeting BH3-Domain Anti-Apoptotic Proteins with GX15-070 Decreases DNA Synthesis, Induces Cell Death and Sensitizes Rituximab-Sensitive and Resistant Non-Hodgkin’s Lymphoma Cell Lines to the Anti-Tumor Activity of Chemotherapy Agents.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2523-2523
Author(s):  
Francisco J. Hernandez-Ilizaliturri ◽  
Arshad Iqbal ◽  
Naheed Alam ◽  
Seema Bhat ◽  
Scott Olejniczak ◽  
...  
Keyword(s):  
Cell Death ◽  
Dna Synthesis ◽  
Cell Lines ◽  
Drug Exposure ◽  
Chemotherapy Resistance ◽  
Bh3 Domain ◽  
Apoptotic Proteins ◽  
Chemotherapy Agents ◽  
Anti Tumor Activity

Abstract GX15-070 is a potent pan-bcl-2 inhibitor with known activity against chronic lymphocytic leukemia (CLL) cells and mantle cell lymphoma (MCL) cell lines, currently undergoing phase I testing. Bcl-2 over-expression is associated with chemotherapy resistance and correlates with a poor clinical outcome in diffuse large B-cell lymphoma. Recently, we demonstrated that acquisition of rituximab resistance is associated with deregulation of BH3-domain pro- and anti-apoptotic proteins. This leads to concomitant resistance to multiple chemotherapy agents. Targeting BH3-domain anti-apoptotic proteins with GX15-070 is an attractive strategy to potentially overcome acquired biologic and/or chemotherapy resistance. To this end we studied the effects of GX15-070 in a panel of rituximab-sensitive (RSCL) and rituximab-resistant cell lines (RRCL). Resistant clones were generated by chronic exposure of Raji, RL or DHL-4 cells to escalating doses of rituximab with (4RH) or without (2R) human complement. Functional assays (e.g. ADCC and CMC assays) demonstrated a significant decrease in rituximab sensitivity in RRCL. In addition, resistance to chemotherapy agents (CDDP, doxorubicin, vincristine, etc.) was demonstrated in RRCL. Lymphoma cells were exposed in vitro to GX15-070 (0 to 20mM) with or without CDDP (0 to 10mM) or Doxorubicin (0 to 1mM). Following a 24 and a 48 hour period of drug exposure: induction of apoptosis and the percentage of viability was determined by flow cytometric analysis, Western blotting and trypan-blue staining techniques. In addition, changes in DNA synthesis and cell proliferation following drug exposure were performed using standard [3H]-thymidine incorporation assays. GX15-070 induced a dose-dependent cell death and decrease in DNA synthesis in all the cell lines tested (both RSCL and RRCL). Up to 75% of cell death was observed in all cell lines exposed to 20mM of GX15-070. Anti-tumor activity was seen even at the lowest tested dose of GX15-070 (2mM, 20–25% death cells). Incubation of RSCL and RRCL with 2 or 5mM of GX15-070 induced synergistic cytotoxic and anti-proliferative effects when combined with CDDP and doxorubicin. The IC50 of CDPP and doxorubicin was decrease ten-fold by the concomitant in vitro exposure to GX15-070 in all cell lines tested, including RRCL. Our data demonstrates that GX15-070 is active against both RSCL and RRCL and augments the anti-tumor activity of chemotherapy agents. These results strongly suggest that GX15-070 added to systemic chemotherapy is a potentially valuable and novel therapeutic strategy in the treatment of B-cell NHL.

scholarly journals Cell Death in Escherichia coli dnaE(Ts) Mutants Incubated at a Nonpermissive Temperature Is Prevented by Mutation in the cydA Gene

2004 ◽  
Vol 186 (7) ◽  
pp. 2147-2155 ◽  
Author(s):  
Bernard Strauss ◽  
Kemba Kelly ◽  
Toros Dincman ◽  
Damian Ekiert ◽  
Theresa Biesieda ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Cell Death ◽  
Dna Synthesis ◽  
Dna Content ◽  
Electrophoretic Pattern ◽  
Luria Bertani ◽  
E Coli ◽  
Viable Cells ◽  
Rna And Protein Synthesis ◽  
Transformation Activity

ABSTRACT Cells of the Escherichia coli dnaE(Ts) dnaE74 and dnaE486 mutants die after 4 h of incubation at 40°C in Luria-Bertani medium. Cell death is preceded by elongation, is inhibited by chloramphenicol, tetracycline, or rifampin, and is dependent on cell density. Cells survive at 40°C when they are incubated at a high population density or at a low density in conditioned medium, but they die when the medium is supplemented with glucose and amino acids. Deletion of recA or sulA has no effect. We isolated suppressors which survived for long periods at 40°C but did not form colonies. The suppressors protected against hydroxyurea-induced killing. Sequence and complementation analysis indicated that suppression was due to mutation in the cydA gene. The DNA content of dnaE mutants increased about eightfold in 4 h at 40°C, as did the DNA content of the suppressed strains. The amount of plasmid pBR322 in a dnaE74 strain increased about fourfold, as measured on gels, and the electrophoretic pattern appeared to be normal even though the viability of the parent cells decreased 2 logs. Transformation activity also increased. 4′,6′-Diamidino-2-phenylindole staining demonstrated that there were nucleoids distributed throughout the dnaE filaments formed at 40°C, indicating that there was segregation of the newly formed DNA. We concluded that the DNA synthesized was physiologically competent, particularly since the number of viable cells of the suppressed strain increased during the first few hours of incubation. These observations support the view that E. coli senses the rate of DNA synthesis and inhibits septation when the rate of DNA synthesis falls below a critical level relative to the level of RNA and protein synthesis.

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