CELL PROLIFERATION IN THE PREPUBERTAL MALE RAT ADRENAL CORTEX: AN AUTORADIOGRAPHIC STUDY

1971 ◽  
Vol 49 (4) ◽  
pp. 599-609 ◽  
Author(s):  
N. A. WRIGHT
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Adrenal Cortex ◽  
Tritiated Thymidine ◽  
Autoradiographic Study ◽  
Male Rats ◽  
Male Rat ◽  
General Increase ◽  
Cortical Cells ◽  
Cell Cycle Time

SUMMARY On the basis of labelling indices measured with tritiated thymidine at intervals throughout its thickness, the adrenal cortex of prepubertal male rats has been divided into four compartments. These are called the glomerular, proliferative, fascicular and reticular compartments, respectively. Labelling indices measured for each compartment showed highest values in the glomerular and proliferative compartments, with values of 6·73% and 7·09% respectively. The fascicular compartment showed a lower index of 3·16% while the reticular compartment gave the lowest value of 1·15%. These differences are further reflected in measurements of the mitotic indices for each compartment. The phases of the cell cycle have been measured by pulse-chase analysis in each compartment, and all phases estimated showed an increase in duration as the inner compartments were approached. The duration of interphase DNA synthesis (ts) was found to be shortest in the glomerular and proliferative compartments, with values of 7·45 and 7·73 h, respectively. The fascicular compartment showed lengthening of ts to 8·56 h, and the reticular compartment gave the highest value of 9·21 h. Similarly, the values obtained for G2 (the post-DNA synthetic interval) and tm (the duration of mitosis), and a calculated value of the cell cycle time all showed a general increase in duration from the outer to the inner compartments. The relation of these results to theories of adrenocortical cytogenesis is discussed, and it is suggested that the differences in cell cycle components can best be explained by the inward migration of cortical cells from the outer compartments.

EFFECT OF DEXAMETHASONE ON CELL POPULATION KINETICS IN THE ADRENAL CORTEX OF THE PREPUBERTAL MALE RAT

1974 ◽  
Vol 62 (3) ◽  
pp. 527-536 ◽  
Author(s):  
N. A. WRIGHT ◽  
D. R. APPLETON ◽  
A. R. MORLEY
Keyword(s):  
Cell Cycle ◽  
Latent Period ◽  
Adrenal Cortex ◽  
Direct Action ◽  
Tritiated Thymidine ◽  
Labelling Index ◽  
Male Rats ◽  
Male Rat ◽  
Rate Of Increase ◽  
Continuous Labelling

SUMMARY The effect of a single injection of dexamethasone on adrenocortical cell proliferation was studied in prepubertal male rats using tritiated thymidine. After a short latent period, all zones of the adrenal cortex showed a rapid decrease in both labelling and mitotic indices. After a prolonged period when very low indices were apparent, there was a rapid rise in both proliferative indices with most zones showing a considerable increase above control values. A more detailed study of the initial depression showed that after a latent period of about 5 h the labelling index fell approximately 8 h before the mitotic index. This differential response in the labelling and mitotic indices was consistent with a block in the cell cycle late in the pre-DNA synthetic interval of the cell cycle (G1), with cells being prevented from entering DNA synthesis. This hypothesis was also supported by an experiment involving continuous labelling of control and dexamethasone-treated animals; again after a latent period of 5–6 h, the rate of increase of the continuous labelling index fell as cells became blocked in late G1. By analogy with other tissues, results are interpreted in terms of a direct action of dexamethasone on adrenocortical cells; this steroid-sensitive step in the cell cycle may be important in the control of growth in the adrenal cortex.

Stem cell studies of human malignant brain tumors

1985 ◽  
Vol 63 (3) ◽  
pp. 426-432 ◽  
Author(s):  
Bertrand Pertuiset ◽  
Dolores Dougherty ◽  
Carlos Cromeyer ◽  
Takao Hoshino ◽  
Mitchel Berger ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Brain Tumors ◽  
Tritiated Thymidine ◽  
Early Passage ◽  
Cell Cycle Time ◽  
Content Type ◽  
Cell Kill ◽  
Fine Print

✓ The proliferation kinetics were studied in early-passage cultures of cells from 13 human malignant brain tumors and two specimens of normal brain under conditions similar to those used in clonogenic cell-survival studies. Autoradiography was performed in all but four cases to estimate the fraction of cells actively replicating deoxyribonucleic acid (DNA), the approximate cell cycle time, and the effect of low-dose tritiated thymidine on cell proliferation. The mean tumor cell doubling time (TD) was 53 hours for five glioblastomas, 46 hours for two ependymomas, and 83 hours for two medulloblastomas. A gliosarcoma grew fastest (TD = 22 hours) in culture and a pilocytic astrocytoma grew slowest (TD = 144 hours). The approximate cell cycle time ranged from 1 to 2.5 days for all tumors tested. This suggests that chemotherapeutic agents that predominantly kill proliferating cells should be administered in vitro for at least 2 to 2.5 days to achieve maximum cell kill. The approximate growth fraction ranged from 0.65 to 0.96 for all tumors except for the two medulloblastomas and the pilocytic astrocytoma, which had growth fractions of 0.34 and 0.35, respectively. Most laboratories investigating the chemosensitivity of primary or early-passage human tumor cells require that 40% to 70% of cells be killed to consider a drug active in vitro. The results of this study suggest that the cell-cycle-specific agents cannot achieve a high enough cell kill to be considered active for some tumors that grow slowly in culture. An estimate of the in vitro growth rate is necessary to reliably interpret cell-survival results with such agents. Tritiated thymidine appeared to slow cell proliferation in some of the cultures, presumably as a result of radiation-induced DNA damage caused by tritium that had been incorporated into DNA. The degree to which cell growth was slowed in individual tumors correlated with the patient's clinical response to radiation therapy and postoperative survival time.

Comparison of Multiple Injections with Continuous Infusion of Tritiated Thymidine, and Estimation of the Cell Cycle Time

1969 ◽  
Vol 5 (3) ◽  
pp. 575-582
Author(s):  
W. K. BLENKINSOPP ◽  
C. W. GILBERT
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Continuous Infusion ◽  
Cycle Time ◽  
Squamous Epithelium ◽  
Tritiated Thymidine ◽  
Intraperitoneal Administration ◽  
Cell Cycle Time ◽  
Multiple Injections ◽  
Stratified Squamous Epithelium

Labelled nuclei were counted in stratified squamous epithelium in mice killed after 24 h intraperitoneal administration of tritiated thymidine to label cells synthesizing deoxyribonucleic acid. Multiple injections produced the same result as an infusion of tritiated thymidine given after 24 h infusion of saline, but infusion of tritiated thymidine alone produced a different result. Thus, cell proliferation was depressed during the first 24 h of continuous infusion but was normal during the second 24 h. Comparison of proliferation of the oesophageal epithelium at the level of the thyroid and at the level of the diaphragm showed no difference between the two. Comparison of male with female mice given 72-h infusions of tritiated thymidine showed that cell proliferation occurred at the same rate in both. The cell cycle time was estimated in the epithelium of the oesophagus and tongue by comparison of mice given a single injection with mice given multiple injections of tritiated thymidine.

scholarly journals Differences in cell cycle characteristics among patients with acute nonlymphocytic leukemia

Blood ◽  
1987 ◽  
Vol 69 (6) ◽  
pp. 1647-1653 ◽  
Author(s):  
A Raza ◽  
Y Maheshwari ◽  
HD Preisler
Keyword(s):  
Cell Cycle ◽  
Tritiated Thymidine ◽  
S Phase ◽  
Total Cell ◽  
Acute Nonlymphocytic Leukemia ◽  
Cell Cycle Time ◽  
Myeloid Leukemias ◽  
History Of

The proliferative characteristics of myeloid leukemias were defined in vivo after intravenous infusions of bromodeoxyuridine (BrdU) in 40 patients. The percentage of S-phase cells obtained from the biopsies (mean, 20%) were significantly higher (P = .00003) than those determined from the bone marrow (BM) aspirates (mean, 9%). The post- BrdU infusion BM aspirates from 40 patients were incubated with tritiated thymidine in vitro. These double-labeled slides were utilized to determine the duration of S-phase (Ts) in myeloblasts and their total cell cycle time (Tc). The Ts varied from four to 49 hours (mean, 19 hours; median, 17 hours). Similarly, there were wide variations in Tc of individual patients ranging from 16 to 292 hours (mean, 93 hours; median, 76 hours). There was no relationship between Tc and the percentage of S-phase cells, but there was a good correlation between Tc and Ts (r = .8). Patients with relapsed acute nonlymphocytic leukemia (ANLL) appeared to have a longer Ts and Tc than those studied at initial diagnosis. A subgroup of patients at either extreme of Tc were identified who demonstrated clinically documented resistance in response to multiple courses of chemotherapy. We conclude that Ts and Tc provide additional biologic information that may be valuable in understanding the variations observed in the natural history of ANLL.

EFFECTS OF STILBOESTROL ON GROWTH HORMONE SECRETION AND PITUITARY CELL PROLIFERATION IN THE MALE RAT

1971 ◽  
Vol 51 (3) ◽  
pp. 473-481 ◽  
Author(s):  
H. M. LLOYD ◽  
J. D. MEARES ◽  
JOAN JACOBI ◽  
FRANCES J. THOMAS
Keyword(s):  
Growth Hormone ◽  
Cell Proliferation ◽  
Mitotic Activity ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Mean Value ◽  
Pituitary Cell ◽  
Male Rats ◽  
Male Rat ◽  
Serum Growth Hormone

SUMMARY A single 12 mg dose of stilboestrol dipropionate given to 100-day-old male rats resulted in increased pituitary mitotic activity, pituitary weight and serum growth hormone; the latter rose from a mean value of 20 ng/ml to a maximum of 342 ng/ml 9 days later. Serum growth hormone and pituitary mitotic activity then gradually diminished but were still slightly increased on day 28. Serum growth hormone and pituitary weight were significantly correlated during the periods of rapidly rising and of sustained high levels of serum growth hormone. Indices of mitotic activity were correlated with serum growth hormone during the periods of rapidly rising and of falling levels of serum growth hormone.

Mediators of the mitogenic action of human V1vascular vasopressin receptors

2000 ◽  
Vol 279 (5) ◽  
pp. H2529-H2539 ◽  
Author(s):  
Marc Thibonnier ◽  
Doreen M. Conarty ◽  
Christine L. Plesnicher
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Protein Kinase ◽  
Dna Synthesis ◽  
Cell Cycle Progression ◽  
Tritiated Thymidine ◽  
Chinese Hamster ◽  
Mitogen Activated Protein Kinase ◽  
Thymidine Uptake ◽  
Mitogenic Action

Arginine vasopressin (AVP) activation of V1 vascular receptors (V1Rs) stimulates cell growth and proliferation in different tissues via cellular signaling pathways that remain to be identified. To explore the intracellular mediators of the mitogenic action of V1R, Chinese hamster ovary (CHO) cells were stably transfected with the human V1R cDNA clone we isolated previously. We assessed AVP effects on kinase activation (immunoblotting with phosphospecific antibodies), DNA synthesis (tritiated thymidine uptake), cell cycle progression (flow cytometry analysis after nuclear labeling with propidium iodide), and cell proliferation (conversion of the colorimetric reagent MTS) in the presence or absence of various pathway inhibitors. AVP stimulation of V1Rs leads to the phosphorylation of several kinases, an increase in DNA synthesis, a progression through the S and G2–M phases of the cell cycle, and an increase in cell proliferation. The mediators of the mitogenic action of V1R activation included calcium mobilization, coupling to a Gq protein, and the simultaneous and parallel activation of several kinases, mainly calcium/calmodulin-dependent kinase II, phosphatidylinositol 3 kinase, protein kinase C, and p42/p44 mitogen-activated protein kinase.

CHANGES IN CELL PROLIFERATION RATE IN MOUSE UTERINE EPITHELIUM DURING CONTINUOUS OESTROGEN TREATMENT

1974 ◽  
Vol 61 (1) ◽  
pp. 117-121 ◽  
Author(s):  
AUDREY E. LEE ◽  
L. A. ROGERS ◽  
GAIL TRINDER
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Dna Synthesis ◽  
Mitotic Index ◽  
Cycle Time ◽  
Luminal Epithelium ◽  
Cell Cycle Time ◽  
Oestrogen Treatment ◽  
Probability Of Transition ◽  
The Mean

SUMMARY Fraction of labelled mitoses (FLM) curves were constructed for mouse uterine luminal epithelium during oestradiol treatment; on day 2 when mitosis was high, and on days 4 and 9 when mitosis was low. No difference was found between the duration of DNA synthesis on these 3 days. The distance between the first and second peaks, usually taken as an estimate of the mean cell cycle time, did not change significantly between days 2 and 4, although the labelling index fell from 38 to 8%. The second peaks of the FLM curves became progressively lower on the three days examined, which was consistent with the interpretation that there was a reduction in the probability of transition of cells from G1 (the post-mitotic period) into the replicative phase of the cell cycle, resulting in the observed fall in mitotic index.

AN AUTORADIOGRAPHIC STUDY ON THE LOCALIZATION OF ANDROGEN IN THE PROSTATE GLAND AND THE SEMINAL VESICLES OF THE MALE RAT

1970 ◽  
Vol 63 (2) ◽  
pp. 207-215 ◽  
Author(s):  
Kjell J. Tveter
Keyword(s):  
Epithelial Cells ◽  
Prostate Gland ◽  
Autoradiographic Study ◽  
Seminal Vesicles ◽  
Radioactive Material ◽  
Male Rats ◽  
Male Rat ◽  
Selective Localization ◽  
Qualitative Pattern

ABSTRACT The distribution of radioactive material in the prostate gland and the seminal vesicles has been studied by autoradiography after intramuscular administration of [1,2-3H] testosterone in vivo to adult castrated male rats. Positive autoradiographs were obtained from 7½ min to 8 h after the administration. As early as after 15 min, there appeared to be a selective localization of radioactivity in the epithelial cells, with much of the labelling associated with the nuclei; the stromal labelling was markedly less. This picture was even more significant ½, 1 and 2 h after the injection, when the autoradiographs demonstrated a preferential labelling of the nuclei of the epithelial cells. A distinct labelling of the epithelial cells was also found 8 h after the injection. The same qualitative pattern of distribution of radioactivity was seen in the four prostatic lobes and the seminal vesicles. No significant labelling of the secretions in the glandular lumina was observed.

scholarly journals Interleukin 4 inhibits the proliferation but not the differentiation of activated human B cells in response to interleukin 2.

1988 ◽  
Vol 168 (4) ◽  
pp. 1321-1337 ◽  
Author(s):  
T Defrance ◽  
B Vanbervliet ◽  
J P Aubry ◽  
J Banchereau
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
B Cells ◽  
B Cell ◽  
Tritiated Thymidine ◽  
Interleukin 2 ◽  
Optimal Concentration ◽  
Interleukin 4 ◽  
Aureus Strain ◽  
Igm Antibody

The combined effect of IL-4 and IL-2 on proliferation of anti-IgM antibody or Staphylococcus aureus strain Cowan I (SAC)-preactivated B cells was investigated. It was observed that in most cases, rIL-2 used at optimal concentration induced higher levels of tritiated thymidine ([3H]TdR) uptake than rIL-4 used at optimal concentration. When rIL-4 and rIL-2 were added together, it was repeatedly found that B cell proliferation induced by rIL-2 was significantly reduced and was, in most cases, comparable with the proliferation induced by rIL-4 alone. Cell cycle studies demonstrated that rIL-4 significantly reduced the number of cells entering S and G2/M phases of the cell cycle upon rIL-2 stimulation. B cell blasts preincubated for 24 or 48 h with rIL-4 displayed a reduced proliferation in response to rIL-2. In contrast, preculture of resting B cells with rIL-4 did not impair their subsequent proliferation in response to rIL-2 plus insolubilized anti-IgM antibody. This suggests that rIL-4 can only exert its inhibitory effect once B cells have received an activation signal. The differentiative activity of rIL-2 measured on B cell blasts preactivated for 2 d with SAC was not altered by rIL-4, which suggests that rIL-4 did not exert its inhibitory activity on rIL-2-induced B cell proliferation by enhancing rIL-2-mediated differentiation. Delayed addition of a neutralizing anti-IL-4 antiserum demonstrated that a period of contact of at least 24 h between IL-4 and B cell blasts was necessary for the development of the antagonistic effect of IL-4 on IL-2-mediated growth of activated B cells. These data demonstrate that IL-4 antagonizes the B cell growth-promoting effect of IL-2 without affecting the differentiation of preactivated B cells in response to IL-2.

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