bluuebunny/crossref_metadata_2025_split huggingface dataset:
A TECHNIQUE FOR DETERMINING THE PROPORTION OF THE CLONOGENIC CELLS IN S PHASE IN EMT6 CELL CULTURES AND TUMORS
Authors: Rockwell Sara , Frindel Emilia , Tubiana Maurice 
Published: May 2008

AbstractThe survival of cultured EMT6 cells was examined after treatment with hydroxyurea (HU) or high specific activity tritiated thymidine (3H‐TdR). The concentrations of the agents, duration of exposure to the agents, and post‐exposure treatment of the cultures were found to influence the cell survival; the effects of these factors are reported. Conditions were defined under which the proportions of cells killed by HU and by 3H‐TdR were the same and were also the same as the proportion of labeled cells seen on autoradiographs of cultures labeled with small doses of 3H‐TdR. Under these conditions, either 3H‐TdR or HU could be used to determine the proportion of the clonogenic cells in S phase.Single cell suspensions prepared from solid EMT6 tumors were treated in vitro with HU or 3H‐TdR, using the conditions found optimal for each agent with cultured cells. The proportion of the tumor cells killed by treatment with HU in vitro was the same as the proportion killed by HU in vivo and as the proportion labeled by 3H‐TdR in vivo, and incubation of tumor cell suspensions with HU in vitro appeared to provide a valid measurement of the proportion of clonogenic tumor cells in S phase. Incubation of tumor cell suspensions with 3H‐TdR in vitro proved difficult to perform and the results were relatively unreliable because of severe problems with reutilization of 3H‐TdR during the incubation for colony formation.
EFFECT OF METHOTREXATE ON THE CELL CYCLE OF L1210 LEUKEMIA
Authors: GONCHAROVA S. A. , FRANKFURT O. S. 
Published: May 2008

AbstractThe influence of methotrexate (MTX) on the proliferative activity of cells in different phases of cell cycle has been studied. MTX (5 mg/kg) was injected i.p. 3 days after the inoculation of 5 × 106 leukemia cells into F1 (DBA × C57 BL) mice. It was shown that MTX causes degeneration of cells, being in G1‐ as well as in S‐phase at the time of drug injection. Incorporation of 3H‐TdR was suppressed for a period ranging from 2 to 12 hr after MTX administration, which is demonstrated by the decrease in the number of grains per cell. The number of cells labeled after 3H‐TdR injection was also sharply decreased during this period. For a period of 3 until 15 hr after MTX administration the mitotic index decreased significantly as a result of inhibition of DNA synthesis. The blocking of the G1‐S transition was evident during 4 hr after MTX. Thereafter the G1‐S transition proceeds at a rate which is practically equal to that for nontreated controls. MTX did not inhibit transition to mitosis of cells being in G2‐phase and in a very late S‐phase at the time of drug injection.The sensitivity of G1‐cells to the cytocidal effect of MTX shows that for L1210 leukemia cells MTX can be classified as a cycle‐specific drug killing both G1 and S‐cells rather than S‐phase specific agent with self‐limitation.
CELL VOLUME GROWTH AFTER CELL CYCLE BLOCK WITH CHEMOTHERAPEUTIC AGENTS
Authors: Ross Dennis W. 
Published: May 2008

AbstractThe effects of various chemotherapeutic agents on the volume of Chinese hamster V79 fibroblasts and murine lymphoma L5178Y cells were studied by electronic volume spectroscopy. Cells arrested in the division cycle by a chemotherapeutic block continued to grow in volume resulting in abnormally large cells unable to reduce their volume by cell division. This was observed in cells treated with colcemid, vinblastine, excess thymidine, hydroxyurea, ARA‐C, 5‐fluorouracil, actinomycin‐D and bleomycin, but not with puromycin or cycloheximide. Increase in cell volume of blocked cells was correlated with a decrease in cell survival as measured by clonogenic ability. The results suggest the possibility of volume spectroscopy for a rapid in vitro test to determine tumor sensitivity to chemotherapeutic agents and the in vivo monitoring of response to chemotherapy. Mechanisms for increased cell kill by a second agent acting selectively on enlarged cells are considered.
KINETICS OF PHYTOHEMAGGLUTININ STIMULATED LYMPHOCYTES IN CHRONIC LYMPHOCYTIC LEUKEMIA
Authors: JAKSIC B. , PAGLIARDI G. L. , PEGORARO L. 
Published: May 2008

AbstractThe DNA synthesis pattern and several kinetic parameters of in vitro PHA stimulated normal and CLL lymphocytes were determined. The DNA synthesis peak of CLL lymphocytes occurred 2–3 days later than that of normal lymphocytes. The generation time, estimated by the labeled mitoses method, was found to be 28 hr and 20 hr for CLL and normal lymphocytes respectively. This difference was mainly due to longer S and Gt periods. It was also shown that both CLL and normal lymphocytes divide several times. These data were confirmed by the chromatid labeling pattern and by the halving of the grains and the double labeling techniques. By combining continuous and pulse labeling the growth fraction of CLL lymphocytes was found to be progressively increasing, because of the recruitment of new cells in cycle, from the third day of culture. Therefore the delayed peak of DNA synthesis of CLL lymphocytes was caused by a longer cell cycle and by a longer pre‐replicative phase.
EFFECT OF VARIOUS DOSES OF ESTROGEN TO BALB/cCrgl NEONATAL FEMALE MICE ON MAMMARY GROWTH AND BRANCHING AT 5 WEEKS OF AGE
Authors: Warner M. R. 
Published: May 2008

AbstractHigh doses of 17β‐estradiol given newborn mice the first 5 days of life had no effect on mammary growth at 3 weeks of age whereas glands measured at 5 weeks of age displayed marked dose‐dependent differences in area and branching.The number of duct branches increased significantly as the estrogen dose was raised from the 25 μg threshold to 35 or to 70 μg. Ratios between area and branching remained constant under all experimental conditions.Regional, dose‐dependent, differences in gland‐pair response were also observed at 5 weeks. Mammary gland pairs differed significantly in several growth parameters. The third gland pair was smaller in area and had fewer branches, but the opposite was true of the second and fourth gland pairs. Systemic injection of high doses of 17β‐estradiol into neonates reduced differences in growth parameters between gland pairs.
ANALYSIS OF CELL CYCLE COMPARTMENTS OF HEPATOCYTES AFTER PARTIAL HEPATECTOMY
Authors: Mrabes Hartmut , Wirsching Rainer , Tuczek Heinz‐Volker , Iseler Gerd 
Published: May 2008

AbstractAn analysis of cell kinetic parameters as a function of intralobular localization of hepatocytes was performed using autoradiographic methods to obtain a basis for a quantitative description of cell cycle compartments after partial hepatectomy.The influx into the S compartment revealed a maximum in a lobular zone not immediately adjacent to the portal tract, with a decrease towards the perivenous and periportal area of the lobule. The maximum influx was found in the intermediate zone at 34 hr and a lower one in the perivenous parts of the lobule at 40 hr. The influx pattern at 56 hr was similar to the situation at 18 hr.The fraction of labelled mitoses in the whole liver and in subunits of the lobule disclosed a constant duration of S whereas the duration of G2+ M was prolonged from the periportal to the perivenous zone.A graphical model of kinetic events after partial hepatectomy is proposed, which describes the sizes of the various cell cycle compartments; the model successfully predicted the results of a continuous labelling experiment.
CELL KINETICS OF A CHONDROSARCOMA
Authors: Dawson Anne , Kember N. F. 
Published: May 2008

AbstractThe cell kinetics of the transplantable DC‐II mouse chondrosarcoma have been studied by the pulse labelled mitoses method. The analysis gave the following estimates for the phases of the cell cycle: G, 10‐5 hr; S, 9‐5 hr; G2, 4 hr with an intermitotic time of 23‐5 hr. Consideration of the overall growth of the tumour indicated that the growth fraction and cell loss factor both had values of about 0–5. The results are compared with cell kinetic data from sarcomas and other cartilage tissues.
REGENERATIVE PROLIFERATION OF MOUSE EPIDERMAL CELLS FOLLOWING ADHESIVE TAPE STRIPPING
Authors: Clausen O. P. F. , Lindmo T. 
Published: May 2008

AbstractThe proliferating cells of mouse epidermis (basal cells) can be separated from the non‐proliferating cells (differentiating cells) (Laerum, 1969) and brought into a mono‐disperse suspension. This makes it possible to determine the cell cycle distributions (e.g. the relative number of cells in the G^ S and (G2+ M) phases of the cell cycle) of the basal cell population by means of micro‐flow fluorometry. To study the regenerative cell proliferation in epidermis in more detail, changes in cell cycle distributions were observed by means of micro‐flow fluorometry during the first 48 hr following adhesive tape stripping. 3H‐TdR uptake (LI and grain count distribution) and mitotic rate (colcemid method) were also observed. An initial accumulation of G2 cells was observed 2 hr after stripping, followed by a subsequent decrease to less than half the control level. This was followed by an increase of cells entering mitosis from an initial depression to a first peak between 5 and 9 hr which could be satisfactorily explained by the changes in the G2 pool. After an initial depression of the S phase parameters, three peaks with intervals of about 12 hr followed. The cells in these peaks could be followed as cohorts through the G2 phase and mitosis, indicating a partial synchrony of cell cycle passage, with a shortening of the mean generation time of basal cells from 83‐3 hr to about 12 hr. The oscillations of the proportion of cells in G2 phase indicated a rapid passage through this cell cycle phase. The S phase duration was within the normal range but showed a moderate decrease and the Gj phase duration was decreased to a minimum. In rapidly proliferating epidermis there was a good correlation between change in the number of labelled cells and cells with S phase DNA content. This shows that micro‐flow fluorometry is a rapid method for the study of cell kinetics in a perturbed cell system in vivo.
RELATIONSHIP OF NUTRITIONAL FACTORS TO IN VITRO TUMOR CELL GROWTH AND CYTOTOXICITY PRODUCED BY CYTOSINE ARABINOSIDE
Authors: Momparler Richard L. , Goodman Joel 
Published: May 2008

ABSTRACTThe in vitro relationship between nutritional factors, proliferative status of tumor cells, and the cytotoxic action of cytosine arabinoside (ara‐C) was investigated. The reduction in the concentration of only one essential amino acid, L‐isoleucine, in the growth medium of A(T1)Cl‐3 hamster fibrosarcoma cells decreased DNA synthesis in this cell population and slowed the rate of progression of G1 phase cells into S phase of the cell cycle. The complete omission of isoleucine from the growth medium blocked the progression of G1 phase cells into S phase and prevented the cytotoxic action of ara‐C. The addition of isoleucine to the isoleucine‐deprived cells permitted these cells to enter the S phase and restored their sensitivity to the cytotoxic action of ara‐C. When G1 phase cells were placed in a medium containing reduced levels of all the amino acids and vitamins there was a prolongation of the G1 phase. Since medium with low levels of amino acids produced a delay in the entry of G1 phase cells into the S phase, the time interval in which these cells were most sensitive to the cytotoxic action of ara‐C was different for G1 phase cells placed in medium with adequate levels of all the amino acids. These in vitro data indicate that nutritional factors can markedly effect the proliferation of tumor cells and the cytotoxic action of ara‐C.
SPECIFIC CHALONE INHIBITION OF THE REGENERATION OF THE JB‐1 ASCITES TUMOUR STUDIED BY FLOW MICROFLUOROMETRY
Authors: Bichel P. , Barfod N. M. 
Published: May 2008

ABSTRACTThe variation in the DNA distribution in the JB‐1 and the Lla2 ascites tumour was investigated by means of flow microfluorometry (FMF) in the plateau stage and during the initiation of the regeneratave growth induced by percutaneous aspiration. The study showed that a considerable influx of cells with G1 DNA content into the S phase occurred in both tumours about 10 hr after aspiration.In the JB‐1 tumour, these initial regenerative changes could be reversibly blocked by injections of cell‐free plateau JB‐1 ascitic fluid or an ultrafiltrate of this ascites. In contrast to these observations no delay in the regenerative changes was observed in the Lla2 tumour after treatment with JB‐1 ascites or the ultrafiltrate.The study supports the assumption of a specific growth regulation of the JB‐1 ascites tumour and emphasizes the suitability of FMF analyses in cell‐kinetic studies in which short‐term fluctuations take place in the distribution of cells with different DNA content.
EFFECTS OF PRE‐IRRADIATION ON ISOGENEIC AND SEMI‐ISOGENEIC CFU GROWTH: A STUDY ON GENETIC RESISTANCE
Authors: Buurman W. A. , Bruggen Ivonne van 
Published: May 2008

ABSTRACTThe genetic resistance to a parental bone marrow transplant as demonstrated, when transplantation was performed early after irradiation, failed to occur if the interval between irradiation and transplantation was increased to 4 days. A similar radiation induced weakening of genetic resistance to a parental bone marrow graft in spleen and bone marrow could be demonstrated in mice, which had been irradiated with a sublethal dose at 7 days prior to the lethal irradiation and transplantation. The pre‐irradiation of the recipient with a sublethal dose induced an enhancement of the growth in spleen and bone marrow of isogeneic transplanted CFU. The pre‐irradiation of a single tibia also resulted in a significant weakening of the resistance in the spleen. The experiments with partial body pre‐irradiation suggested a local effect of the pre‐irradiation, but it could be shown that the enhanced CFU growth is not caused by an enhanced seeding of CFU in pre‐irradiated bone marrow. The role of microenvironment in the phenomenon of genetic resistance is discussed.
SOME PROPERTIES OF A ‘G0’‐MODEL OF THE CELL CYCLE
Authors: Maertelaer V. de , Galand P. 
Published: May 2008

ABSTRACTThe two‐phase (G and C phases) model first proposed by Burns & Tannock (1970) to describe the cell cycle kinetics has the major advantage of requiring only two parameters for a complete description of the kinetic behaviour of populations that are in a steady‐state, or that grow exponentially (with no cell loss from the population).Steady‐state populations were examined in paper I of this series. Exponential populations with no cell loss are investigated here. The model assumes two basic kinetic states—a ‘C’phase which includes S, G2, M and perhaps part of G1, and a ‘G’phase which cells enter after completing the C‐phase and from which either are lost or return to C‐phase randomly. The model assumes that transit time through C‐phase is constant for all cells in the population. An original method is described which allows the determination of two independent parameters of the model from the experimental ‘fraction of labelled mitoses’(FLM) curve. From those two parameters, the ratio of G‐cells among the total number of cells (NG/N) has been calculated for each cell population studied. The range of the NG/N values thus obtained is fairly restricted, and the mean NG/N value for exponential growths is not statistically different from that found in steady‐states considering in that case the only sub‐population of cycling cells (i.e. the cells that will undergo a further mitosis).
EFFECTS OF BLEOMYCIN ON THE EPIDERMAL CONTENT OF GROWTH‐REGULATORY SUBSTANCES (CHALONES)
Authors: Iversen O. H. , Clausen O. P. F. , Elgjo K. , Iversen Ulla M. , Rohrbach R. 
Published: May 2008

ABSTRACTHairless male mice were given 2 mg Bleomycin i.p. on two successive days. At different time intervals from 1 to 10 days after the last Bleomycin injection, groups of animals were killed and water extracts of homogenized skin were made.These extracts, supposed to contain the epidermal G1 and G2 chalones, were injected into female hairless mice, and their growth inhibitory potency determined by two methods. 5 mg of lyophilized crude skin extract were injected i.p. together with Colcemid, and the animals killed 4 hr later. The number of Colcemid‐arrested mitoses was determined, and was considered to be a measure of the G2 inhibitor present in the skin extracts. 10 mg of the same extracts were injected i.p., and these animals also got 3H‐TdR i.p. 12 hr later, and were killed after a subsequent 30 min. The epidermal LI was determined, and was considered to be a measure of the epidermal G1 factor in the skin extracts. The results obtained were compared to the effect of Bleomycin alone and to the effects of skin extracts from non‐Bleomycin‐treated animals.The results show that Bleomycin provoked slight alterations in the growth‐inhibitory potency of the G1 chalone, whereas significant effects were seen in the G2 chalone. There was an increased amount of growth‐inhibiting factors on days 2 and 3, and on days 8–10.The results are discussed and it is concluded that the most probable hypothesis is that Bleomycin, in addition to its known inhibitory effect on epidermal cell proliferation, exerts growth inhibition by accumulation of cells with high growth inhibitory potency. An initial, additional direct effect of Bleomycin on the chalone system cannot be excluded.
THE EFFECT OF A SINGLE INJECTION OF HYDROXYUREA ON CELL POPULATION KINETICS IN THE SMALL BOWEL MUCOSA OF THE RAT
Authors: Al‐Dewachi H.S. , Wright N. A. , Appleton D. R. , Watson A. J. 
Published: May 2008

ABSTRACTThe effect of a single injection of hydroxyurea (HU) on cell population kinetics in the jejunal crypt of the rat was studied using autoradiography with tritiated thymidine and metaphase arrest with vincristine. HU appeared to act selectively on cells in the S phase producing inhibition of DNA synthesis and cell death. The deficit in proliferating cells was made good by a decrease in cell cycle time and an increase in growth fraction. Particular attention was paid to the basal, slowly cycling (and possibly clonogenic) crypt cells; early in the recovery sequence an increase in cell production rate was found in the base of the crypt.It is proposed that basal crypt cells, having survived cycle‐specific insult because of long cell cycle times, proceed to repopulate the depleted proliferative compartment.
THE EFFECTS OF RED BLOOD CELL EXTRACTS ON THE PROLIFERATION OF ERYTHROCYTE PRECURSOR CELLS, IN VIVO
Authors: Lord B. I. , Shah G. P. , Lajtha L. G. 
Published: May 2008

ABSTRACTSaline incubation extracts of mature erythrocytes were assayed in vivo by a variety of techniques in order to study their ability to modify the proliferation of maturing erythroid cells. Using comparable extracts from granulocytes and lymphocytes, the specificity of the effect of the red cell extract for erythroid cells was confirmed by measurement of autoradiographic labelling indices, radio‐iron incorporation and spleen colony growth. The erythroid cells were found to be very sensitive to the effects of the extract, as little as 10 μg per mouse producing a maximum effect on iron incorporation. It was found that the extract does not block erythroid cell proliferation completely but simply lengthens the cell cycle, mainly by increasing the G1 phase of the cycle. There was no effect on the committed erythroid precursor cells. The in vivo activity, specificity and non‐toxicity to the cells, together with the cells' sensitivity to red cell extract suggest, therefore, that this inhibitor may play a physiological role in the control of red cell production.
PROPERTIES OF THE H‐4‐II‐E TUMOR CELL SYSTEM
Authors: Kovacs C. J. , Evans M. J. , Hopkins H. A. 
Published: May 2008

ABSTRACTThe growth and cell proliferation characteristics of the H‐4‐II‐E cell line, giving rise to hepatoma H‐4‐II‐E when inoculated into male ACI rats, were studied in vitro. Following seedling of 2 × 103 cells into culture dishes, exponential cell growth occurs in cultures fed both at 24 hr and 48 hr intervals with a population doubling time of 18.4 hr. Plateau phase growth conditions are established on day 7 and day 5 for cultures fed at 24 hr and 48 hr intervals respectively. Both the plateau phase cell density and the maintenance of plateau phase appear dependent on the frequency of feeding. For cultures fed daily, the transition from exponential growth to plateau phase results from both a reduction in the number of proliferating cells (99% v. 35%) as well as an elongation of the cell cycle (17.7 hr v. 128.4 hr). The cell proliferation characteristics of the culture are further discussed in reference to both cell growth and feeding schedules of other cell lines.
INCREASED CELL PROLIFERATION WITH PERSISTENCE OF CIRCADIAN RHYTHMS IN HAMSTER CHEEK POUCH NEOPLASMS
Authors: Izquierdo J. N. 
Published: May 2008

ABSTRACTSquamous cell neoplasms induced by repeated topical application of 7,12‐dimethyl‐benz(a)anthracene in Syrian hamster cheek pouch exhibited circadian rhythms of DNA synthesis and mitotic activity. Fluctuations in the fractions of cells in mitosis and DNA synthesis observed in the tumors were approximately in phase with the circadian rhythms from normal precursor epithelium, indicating that some degree of host physiologic modulation persists during neoplastic growth. The labeling (thymidine‐3H) and mitotic indices of neoplasms were considerably higher than normal throughout the 24 hr period. The duration of the neoplastic S phase—measured from the PLM curve—was 30% shorter than normal; G2 did not show detectable variation. The data demonstrated that chemically induced squamous cell neoplasms had markedly increased rates of cell production. It is postulated that applications of a carcinogen upon a cell‐renewing population generate a multicompartmental cytokinetic imbalance in which: (1) a higher proportion of G0 cells is stimulated to enter the cycle; (2) the duration of the cell cycle is shortened; (3) the regulatory mechanisms fail to stimulate an accelerated rate of differentiation to compensate for the overproduction of cells; and (4) the state of proliferative hyperactivity becomes stable. An oncogenic cytokinetic mechanism based solely on a persistent decrease in cell loss (differentiation) is ruled out by the present investigation, at least for squamous cell neoplasms.
CELL CYCLE TIME DETERMINATIONS BASED ON LIQUID SCINTILLATION COUNTING OF 3H‐TdR LABELED MITOTIC CELLS
Authors: Barranco S. C. , Haenelt B. R. , Bolton W. E. 
Published: May 2008

ABSTRACTFollowing a 10 min pulse labeling with 3H‐TdR, flasks of asynchronous monolayer cultures of Chinese hamster ovary cells were subjected to mitotic selection at 2 hr intervals. The mitotic index of the selected populations was always greater than 90%. Counts per min per cell obtained by liquid scintillation counting were plotted versus time after the pulse label. Comparisons were made between cycle times obtained by the mitotic‐scintillation counting method and by the standard per cent labeled mitosis technique. The resulting curves were used for calculations of the cell cycle times and the lengths of G1, S, G2 and M phases of the cell cycle. There was less than 2% difference in the cell cycle times obtained using the scintillation method as compared to times calculated from autoradiographic data obtained from individual petri dishes.The mitotic‐scintillation counting technique is simple, accurate and rapid and allows the calculation of the cell kinetics parameters within 1 hr of the end of the experiment.