bluuebunny/crossref_metadata_2025 huggingface dataset:
TOPOGRAPHY OF DNA SYNTHESIS IN THE MAMMARY GLAND OF THE C3H MOUSE AND ITS CONTROL BY OVARIAN HORMONES: AN AUTORADIOGRAPHIC STUDY
Authors: Bresciani Francesco
Published: May 2008

Tritium‐labelled thymidine was injected 45 min before sacrifice into virgin female C3H/HeJ mice 7–23 weeks of age, as well as into 10‐week‐old mice which had been ovariectomized and treated daily with 1 μg of oestradiol‐17β and/or 1 mg of progesterone. Autoradiographs were made of squash preparations of the mammary glands, stained by Feulgen's method. The following results were obtained: (1) During normal development of the gland, cells synthesizing DNA are abundant in terminal buds and virtually absent in duct epithelium. Hence ductal growth takes place by the addition of cells produced in the terminal end structures. (2) At 5–6 months, when mammary growth has ceased, a considerable number of cells synthesizing DNA can still be found in alveoli, though not in duct epithelium. Hence the alveolar cells constitute a renewal population in the adult virgin. Because they maintain the potentiality to divide, duct cells are a G0 population. (3) Ovariectomy results in arrest of DNA synthesis within 3–5 days. Both oestradiol and progesterone restore DNA synthesis in alveoli but only progesterone is able to induce DNA synthesis in duct epithelium, and the differentiation of terminal buds into alveoli. This finding provides an explanation for the resumed proliferation of duct cells in pregnancy. (4) The number of cells engaged in DNA synthesis varies considerably among identical structures within the same gland. This may be due either to synchrony of cell replication and/or to fluctuations of proliferative activity in the gland.
AGE‐DEPENDENT TOXIC PROPERTIES OF ACTINOMYCIN D AND X‐RAYS IN CULTURED CHINESE HAMSTER CELLS
Authors: Elkind M. M. , Sakamoto K. , Kamper C.
Published: May 2008

A comparative study was made of the toxic properties of actinomycin D and X‐rays using synchronized populations of Chinese hamster cells cultured in vitro. X‐irradiated cells are most resistant in the latter half of the DNA synthetic period (late S). While cells treated with actinomycin D appear to go through a survival maximum at the same age, they are most resistant after the completion of DNA synthesis; i.e. in G2 (or G2‐mitosis).

In spite of these differences, we found that actinomycin D damage in late S cells interacts with X‐ray damage. Thus, a common locus for the site of actions of both agents is suggested which may be in or around the genome of a cell in view of the well‐known DNA binding properties of actinomycin D.
METHODS FOR COMPUTING LYMPHOCYTE KINETICS IN MAN BY ANALYSIS OF CHROMOSOMAL ABERRATIONS SUSTAINED DURING EXTRACORPOREAL IRRADIATION OF THE BLOOD
Authors: Sharpe Heather B. A. , Dolphin G. W. , Dawson K. B. , Field E. O.
Published: May 2008

Data on lymphocyte kinetics may be derived in patients undergoing treatment by extracorporeal irradiation of the blood by studying chromosome aberrations induced in their lymphocytes; the aberrations are observed when the lymphocytes are stimulated by phytohaemagglutinin to divide in culture. Two methods of analysis are described, one depends on the total number of dicentrics scored, the other employs the dilution principle, regarding each lymphocyte bearing one or more aberrations as specifically labelled. Two parameters may be calculated: the mean residence time of lymphocytes in the blood and the size of the extravascular pool of lymphocytes in the body. In a patient with Hodgkin's disease, the mean residence time was found to be 4.7–7.5 min and the extravascular pool 800–1070 g.
CELL PROLIFERATION IN NEWLY TRANSPLANTED EHRLICH ASCITES TUMOR CELLS
Authors: Wiebel Friedrich , Baserga Renato
Published: May 2008

Ehrlich ascites tumor cells collected from donor mice on the 5th day after inoculation were injected into the peritoneal cavity of new recipient mice.

Cell cycle times were drastically shortened by transplantation, for instance, the length of the cell cycle from 47 to 21.5 hr, and the duration of S from 26.5 to 16.5 hr.

Transplantation also caused a transient delay of cells in G2 followed by a rapid acceleration and produced an immediate increase in the number of cells in DNA synthesis by about 5–8%.
STUDIES OF HEMATOPOIESIS IN MURINE SPLEENS: SIGNIFICANCE OF HEMATOPOIETIC COLONIES FORMED ON THE SURFACE OF SPLEENS
Authors: Lewis J. P. , O'Grady L. F. , Trobaugh F. E.
Published: May 2008

Conies of hematopoietic tissue are formed in spleens of lethally irradiated mice by the injection of small numbers of hematopoietic cells. Some of these colonies appear as surface colonies, others can be identified only in serial sections of the spleen. The present studies have related the number and cellular composition of total hematopoietic colonies in the murine spleen to their visual recognition on the splenic surface. These studies demonstrate that only 50% of the total colonies in a spleen are recognized as surface colonies and that of those colonies on the surface, approximately 80% contain erythroid elements. At least four factors play important roles in the recognition of hematopoietic colonies as splenic surface colonies: (1) dose of repopulating cells or hematopoietic stem cells injected into the irradiated animal; (2) location of colonies within the spleen; (3) size of colonies; and (4) cellular content of the colonies. These studies demonstrate that surface colony formation reflects primarily erythropoiesis and not total hematopoiesis.
REPOPULATION OF THE BONE‐MARROW STEM‐CELL COMPARTMENT AFTER IRRADIATION*
Authors: Silini G. , Elli R. , Siracusa G. , Pozzi L. V.
Published: May 2008

Bone‐marrow repopulation has been followed as a function of time after a single whole‐body dose of 150 rads X‐rays to (C3H × C57B1)F1 hybrid mice. The number of nucleated cells per bone shaft has been estimated by direct counting and the number of progenitor cells by the exogenous spleen‐colony assay method. Vinblastine was also administered under various schedules of time and dose in an endeavour to distinguish between cycling and dormant cells in the progenitor pool.

The depopulation of total marrow cells induced by Vinblastine proceeds at a comparable rate in irradiated and in normal mice. On the other hand, the depopulation of the colony‐formers is faster in irradiated than in normal animals. The data are interpreted to show that the fraction of cycling progenitor cells is larger in a haemopoietic tissue undergoing numerical expansion.
A CHARACTERIZATION OF THE BOUNDARY BETWEEN THE CYCLING AND RESTING STATES IN ASCITES TUMOR CELLS
Authors: Lala Peeyush K. , Patt Harvey M.
Published: May 2008

Growth deceleration of an Ehrlich ascites tumor with increasing mass is associated with a prolongation of the cell cycle and a decline in the growth fraction. These effects are reversed upon transfer of cells from an older tumor into a new host. Studies were made to locate the stages at which a cell cycle could be suspended or resumed. Transplantation caused a prompt rise in both mitotic and flash H3TdR labeling indices. When all the cells in cycle including mitoses were prelabeled with H3TdR in older tumors, the fraction of labeled mitoses did not decline for a considerable period after transplantation into new hosts. This suggests that the early rise in mitoses is not due to a flow of resting (Go) cells from a G2 store (G2‐Go transition). It appears rather to be a reflection of a lag of the mitotic process relative to other stages during the initial readjustment of the cycle. A prompt rise in flash H3TdR indices in the transplants suggested cell entry into S from either a suspended GI (G1‐Go transition) or a suspended S (S‐Go transition). These possibilities were examined by relating micro‐spectrophotometric estimates of DNA to the cell cycle stage as revealed by H3TdR autoradiography. Since Go cells had DNA values corresponding to GI, it was concluded that decycling or recycling could occur only after mitosis and before DNA synthesis.
AN EVALUATION OF ERYTHROPOIESIS IN THE YOUNG RAT
Authors: Roylance P. J.
Published: May 2008

Estimates of the cell population kinetic parameters have been obtained for the erythroid cells of the young growing rat using the technique of labelled mitoses and these results have been analysed by a computer programme. The phases of the cell cycle for the proliferating cells have been shown to be of shorter duration than generally reported. Together with the differential cell count and initial labelling index these data have enabled estimates of the growth fraction, birthrate, flow rate, number of divisions and transit time to be determined for each compartment.
RECOVERY IN THE MOUSE SPLEEN AFTER SUBLETHAL IRRADIATION
Authors: Petrov R. V. , Koslov V. A. , Seslavina L. S.
Published: May 2008

1. CBA and C57B1 mice were exposed to LD50/30 doses of γ‐radiation and at intervals after irradiation the numbers of haemopoietic colony‐forming units (CFU) and of antibody‐producing cells in the spleen were determined.

2. CFU repression was observed after transfer of non‐irradiated cells to hybrid recipients. However, this repression did not appear until 60 days after irradiation of the donor.

3. The recovery after irradiation of the capacity to inactivate CFUs in spleen cell mixtures was studied. The results suggested that cells which produce 19S antibody are different from those which are reactive against foreign cells.
CELL PROLIFERATION IN THE RAT KIDNEY INDUCED BY FOLIC ACID
Authors: Threlfall G.
Published: May 2008

The changes in proliferative activity of tubular epithelial cells of the rat kidney following a single injection of folic acid (250 mg/kg body weight) have been studied. Autoradiography with tritiated thymidine revealed a large increase in numbers of labelled cells, beginning at about 18 hr, in each of the three kidney zones examined. In the cortex the maximum increase in labelling index (16 times normal) was found at 36 hr whereas that of the outer medulla (34 times normal) occurred at 24 hr; there was no clearly defined peak in the inner medulla, values of up to 36 times normal being found between 24 and 96 hr. These changes were followed several hours later by similar changes in mitotic index in the corresponding zones. All the indices, except the mitotic index of the inner medulla, had returned to normal by 6 days. Comparison of the curves of labelling index and mitotic index in each zone indicated that the number of cells induced to synthesize DNA was approximately similar to the number of cells which subsequently underwent mitosis.

A large increase was also found in the specific activity of DNA extracted from homogenates of whole kidneys from folic acid‐injected rats, again using tritiated thymidine as label. The increase began at about 18 hr, reached a maximum of 16 times normal at 32 hr and returned to normal by 6 days. These changes were similar to those of labelling index in the cortical zone.
THE KINETICS OF LYMPHOCYTE RECIRCULATION WITHIN THE RAT SPLEEN
Authors: Ford W. L.
Published: May 2008

The migration of lymphocytes from the blood into the splenic pulp and the release of lymphocytes from the spleen into the blood was studied by isolating the rat spleen and perfusing it with 15 ml of recirculating, oxygenated blood.

When thoracic duct lymphocytes labelled with tritiated uridine were added to the initial perfusate the concentration of these cells fell exponentially for 2–3 hr and then rose to a flat secondary peak. From this pattern it was inferred that small lymphocytes entered the spleen at a rate proportional to their instantaneous concentration in the perfusate, traversed the splenic pulp and re‐entered the perfusate with a minimum transit time of 2–3 hr. The rate of release of small lymphocytes from the spleen was not influenced by the prevailing concentration of small lymphocytes in the perfusate but probably reflected the rate of migration into the spleen over a period earlier than 2 hr before. The rate of exchange of small lymphocytes between the blood and the intact spleen in vivo was estimated to be about 84 × 106 cells/hr. The size of the intrasplenic pool of recirculating small lymphocytes was probably 400–500 × 106 cells. The rate of migration of small lymphocytes into the spleen was not affected by prior irradiation of the spleen donor. When either of two antigenic materials were added to the perfusate no inhibition of lymphocyte migration into the spleen was noted although the release of lymphocytes from the spleen was diminished by the addition of a large dose of sheep erythrocytes.
THE ACTION OF HYDROXYUREA ON MOUSE L‐CELLS*
Authors: Bacchetti S. , Whitmore G. F.
Published: May 2008

The toxic and inhibitory properties of hydroxyurea (HU) have been studied in asynchronous and synchronized populations of mouse L‐cells. Hydroxyurea is a potent growth inhibitor and appears to be specifically lethal for cells which are in the early part of S phase at the time the compound is introduced. Cells in late S phase, G2, mitosis and G1 appear to progress normally around the cycle in the presence of the compound until they reach the G1/S boundary. There are indications that at least some G1 cells are able to enter the S phase even in the presence of the drug; however their flow into S is much slower than that of control cells and therefore they are killed at a slow rate. Upon prolonged exposure to the drug a second phase of more rapid killing is observed, beginning at about the time division would occur in uninhibited cells. Hydroxyurea exhibits a rapid and marked inhibition on DNA synthesis but its effect on RNA synthesis is much less pronounced and may be a consequence of the inhibition of DNA synthesis. The effects of hydroxyurea on cell viability and DNA synthesis can be partially prevented by the addition of deoxyribonucleosides which in sufficient concentration appear to compete temporarily with the drug. The fact that the protection is only temporary would appear to rule out the hypothesis that the primary mode of action of the drug is the inhibition of the reduction which converts ribonucleotides to deoxyribonucleotides. The data presented in this communication taken together with observations of other workers would appear to suggest that the effect of the drug may be directly on the DNA molecule.
THE EFFECT OF IRRADIATED PLASMA ON NORMAL HUMAN CHROMOSOMES AND ITS RELEVANCE TO THE LONG‐LIVED LYMPHOCYTE HYPOTHESIS
Authors: Scott David
Published: May 2008

The persistence of unstable chromosome‐type aberrations in peripheral blood lymphocytes of irradiated individuals has led to the proposal that some lymphocytes survive for many years in vivo without undergoing mitosis (Fitzgerald, 1964). It has recently been shown, however, that plasma from irradiated individuals can induce chromosomal damage in cultures of normal blood lymphocytes (Hollowell & Littlefield, 1968) even when the plasma donors were irradiated 7 years earlier (Goh & Sumner, 1968). Goh (1968) has therefore suggested that ‘An alternate explanation to the “long‐lived cell” theory proposed by others…would be that a substance is produced or activated by total body irradiation and remains capable of affecting the chromosomes for extensive lengths of time'.

The present results show that a lymphocyte chromosome‐breaking factor can be induced in the plasma of blood irradiated in vitro as well as in vivo. All of the aberrations induced by this ‘plasma factor’and those reported by other workers can be interpreted as being of the chromatid type. Before the long‐lived lymphocyte hypothesis can be brought into serious disrepute, it must be shown that the plasma factor can induce aberrations of the same type as persist after in vivo irradiation (i.e. unequivocal chromosome‐type aberrations, such as dicentrics and rings) and that these can be induced in vivo.
A SIMPLE COMPUTER SIMULATION MODEL FOR GROWING CELL POPULATIONS: ANALYSIS OF SYNCHRONIZED HELA CELL CULTURES
Authors: Tibaux G. , Firket H. , Hopper A. F.
Published: May 2008

A simple simulation model is presented for growing cell populations. It consists of various ‘classes’of cells (usually thirty) with different cell cycle durations. The cells of each class are distributed in ‘compartments’(thirty to fifty) with different ages. A ‘typical cell’of each compartment is chosen at random and its behaviour weighed according to the number of cells of the compartment.

When the parameters for cycle phase durations (G2, S, G1 and M) obtained from Quastler‐Sherman curves on HeLa cell cultures are fed into the model and the initial distribution of cells is randomized according to the law of exponential growth, the model behaves as an exponentially growing culture with near stable values for the percentage of cells in the various phases of the cell cycle. The level of noise due to random sampling is not objectionable.

The behaviour of the model is compared to that of HeLa cultures synchronized by two successive treatments with 2 mM thymidine. While a complete block of S gives very inadequate results, a slowing down of this phase to 25 or 30% of its original speed is enough to simulate all the modifications produced by the thymidine treatment on the cultures. It is not necessary to postulate any other effect.

These biological conclusions are reached in spite of the simplicity of the system. The behaviour of the model stresses the fact that for simulating the actual behaviour of cell populations, some parameters of the cell cycle have to be known with considerable accuracy, others are less critical. The model is compared with other mathematical models of cell populations recently proposed and ways to improve it are discussed.
THE DURATION OF MITOSIS IN THE CRYPTS OF LIEBERKÜHN OF THE TERMINAL ILEUM OF THE ALBINO RAT
Authors: Clarke Rufus
Published: May 2008

The duration of mitosis in the epithelium of the terminal ileum of the adult rat has been determined by counting normal mitotic figures, and colchicine‐metaphases, in Feulgen‐stained squashes of whole, micro‐dissected crypts of Lieberkühn. The duration, which depends on the morphological definition of mitosis adopted, was calculated to be 23 min.

This value is similar to those determined by other authors using other methods, except in the case of tritiated‐thymidine autoradiography, where the reported duration of mitosis is considerably longer. The possibility that this is due to an effect of thymidine on mitosis is discussed.
ABSENCE OF EFFECT OF MULTIPLE INTRAPERITONEAL INJECTIONS ON CELL PROLIFERATION, AND ESTIMATION OF THE CELL CYCLE TIME IN THE EPITHELIUM OF THE OESOPHAGUS AND FORESTOMACH IN MICE, HAMSTERS AND RATS
Authors: Blenkinsopp W. K.
Published: May 2008

Counts of labelled epithelial nuclei in mice given single or multiple injections of tritiated thymidine (to label cells synthesizing deoxyribonucleic acid), either alone or after 24 or 48 hr multiple injections of water, showed that multiple intraperitoneal injections did not disturb normal cell proliferation. The rate of cell proliferation was the same in the epithelium of the oesophagus and forestomach, and in these epithelia there was no difference between mice, hamsters and rats. Cell cycle times were estimated in these epithelia from the number of nuclei labelled in animals given single or multiple injections of tritiated thymidine.
THE COMPARATIVE EFFECT OF BUSULPHAN (‘MYLERAN’) AND AMINOCHLORAMBUCIL ON HAEMOPOIETIC COLONY FORMING UNITS IN THE RAT
Authors: Dunn C. D. R. , Elson L. A.
Published: May 2008

Using the spleen colony assay technique, it has been shown that busulphan (‘Myleran’) in a dose of 10‐2 g/kg (1/2 LD50), causes a marked and prolonged depression (over 90%) in the number of colony forming units per femur (CFU/femur). This depression is apparent before there is any marked reduction of the total cell count per femur and is maximal 2–4 days after an intraperitoneal (i.p.) injection of the drug. It is then followed by a steady recovery, normal values being reached after about 20 days.

In contrast, aminochlorambucil (2·5 x 10‐3) g/kg = 1/2 LD50) although producing a rapid fall in the marrow cellularity has no discernable effect on the CFU/femur.

If, however, a depression of CFUs is first induced by busulphan and, after allowing time for 50% recovery (13 days), aminochlorambucil is now given, a further severe depression of the CFUs/femur occurs resulting in a considerable prolongation of the neutropenia observed in the blood.

The possible implications of this in the mode of action of these two drugs, and in the chemotherapy of leukaemia, are discussed.
STUDIES ON LYMPHOCYTES
Authors: Iorio R. J. , Chanana A. D. , Cronkite E. P. , Joel D. D.
Published: May 2008

Tritiated thymidine was administered to calves continually for 2 to 8 days via the thymic artery in an attempt to label intensively thymic lymphocytes. Heavily labeled cells which had migrated from the thymus were observed in the spleen, lymph nodes and Peyer's patches. Cell maps were made for the various lymphoid tissues and in all cases the majority of labeled thymic cells were found in the ‘thymus dependent areas’of the spleen and lymph nodes. The number of labeled thymic cells per thousand lymphocytes was highest in the ‘thymus dependent areas’. A few labeled thymic cells were seen in or near the post capillary venules. The labeling pattern in the Peyer's patches was different from that in the spleen and lymph nodes. Labeled thymic cells were not observed in the bone marrow.

Heavily labeled cells were not detected in any of the lymphoid tissues of those calves which received continuous intravenous infusion of comparable amounts of tritiated thymidine.
MITOTIC G2 DELAY INDUCED IN SYNCHRONIZED HUMAN KIDNEY CELLS BY UV AND X‐IRRADIATION AND ITS RELATION TO DNA STRAND BREAKAGE, REPAIR AND TRANSCRIPTION
Authors: Scaife J. F.
Published: May 2008

Synchronous populations of human kidney T‐cells have been used to investigate the influence of BUdR incorporation into nuclear DNA on mitotic G2 delay produced by UV or X‐irradiation. By this means true G2 delay could be distinguished from a prolongation of the S‐phase. X‐ray induced mitotic delay is only slightly increased in BUdR containing cells. UV induced mitotic delay is appreciably augmented in cells having incorporated BUdR. These cells show extensive single‐strand breaks in their DNA which is fairly rapidly repaired. Transcription and translation are also appreciably reduced following UV in such cells. It is concluded that mitotic inhibition following X‐irradiation is a result of mechanisms other than the damage to and repair of DNA while mitotic inhibition following UV‐irradiation is primarily related to DNA damage and repair. The specific division proteins synthesized in G2 in these cells constitute only a minor component of the total soluble cell proteins.
EPIDERMAL REGENERATION AFTER CELLOPHANE TAPE STRIPPING OF HAIRLESS MOUSE SKIN
Authors: Hennings Henry , Elgjo Kjell
Published: May 2008

After repeated applications of cellophane tape to the dorsal skin of hairless mice, the proliferative response in the treated epidermis was estimated by three different methods. The mitotic rate was determined in the interfollicular epidermis using the Colcemid technique, and the DNA synthetic activity was estimated after 3H‐thymidine injection by counting labelled interfollicular cells in autoradiographs and by determining the specific activity of epidermal DNA.

An initial 40–50% inhibition of DNA synthesis and mitosis was followed by an increase in the labelling index and the mitotic rate 8–10 hr after tape stripping. By 24 hr, peak values 5–6 times the controls were attained for both parameters. The labelling index and the mitotic rate were nearly normal at 3–4 days, but a second small peak was seen on day 5. Normal values were found on days 6 and 8. A similar pattern of response was found biochemically, but the peak of DNA specific activity was much broader and the extent of the increase was only about half as great as the increase in the labelling index. Possible reasons for these differences are discussed.
EFFECT OF HAIR PLUCKING ON THE KINETICS OF METHYLCHOLANTHRENE‐INDUCED SKIN TUMOURS IN MICE
Authors: Hegazy M. A. , Fowler J. F.
Published: May 2008

Both the latent period and the volume doubling time of 20‐methylcholanthrene‐induced tumours in the skin of SAS/TO mice have been found to be longer for plucked skin than for unplucked skin, even though the cell cycle time of the basal layer cells of the epithelium is much shorter after plucking (50 ± 4 hr) than in unplucked skin (110 ± 10 hr).
ON THE EXISTENCE OF A Go‐PHASE IN THE CELL CYCLE
Authors: Burns F. J. , Tannock I. F.
Published: May 2008

The model is based on the assumption that the cell cycle contains a Go‐phase which cells leave randomly with a constant probability per unit time, γ. After leaving the Go‐phase, the cells enter the C‐phase which ends with cell division. The C‐phase and its constituent phases, the‘true’G1‐phase, the S‐phase, the G2‐phase and mitosis are assumed to have constant durations of T, T1Ts, T2 and Tm, respectively. For renewal tissue it is assumed that the probability per unit time of being lost from the population is a constant for all cells irrespective of their position in the cycle.

The labelled mitosis curve and labelling index for continuous labelling are derived in terms of γ, T, and Ts. The model generates labelled mitosis curves which damp quickly and reach a constant value of twice the initial labelling index, if the mean duration of the Go‐phase is sufficiently long. It is shown that the predicted labelled mitosis and continuous labelling curves agree reasonably well with the experimental curves for the hamster cheek pouch if T has a value of about 60 hr. Data are presented for the rat dorsal epidermis which support the assumption that there is a constant probability per unit time of a cell being released from the Go‐phase.
THE EFFECTS OF LOW CONCENTRATIONS OF ACTINOMYCIN D ON THE PROGRESS OF CELLS THROUGH THE CELL CYCLE
Authors: Rickinson A. B.
Published: May 2008

The progress of L‐cells through the cell cycle in asynchronous and in synchronous culture has been studied at a concentration of actinomycin D which mediates an apparently‘nucleolar‐specific’inhibition of RNA synthesis. Under such conditions, cells may be blocked or seriously delayed in the G1 and G2 phases of the cycle whilst the processes of DNA synthesis and mitosis once initiated, can still occur at control rates. The results show that the sensitivity of a cell to these blocks depends critically upon the position of that cell within the cycle at the time of drug addition. The possible mechanisms of the drug's action are discussed.
THE EFFICIENCY OF THE ASSAY FOR HAEMOPIETIC COLONY FORMING CELLS
Authors: Lahiri S. K. , Keizer H. J. , Putten L. M. van
Published: May 2008

The quantitative efficiency of the spleen colony assay in mice is discussed in the light of recent findings on the kinetics of colony forming cells. Arguments are presented showing that the f factor, the 2 hr CFU recovery fraction in the spleen, markedly over‐estimates the assay efficiency which is the ratio of the numbers of colony forming units and colony forming cells.
EFFECTS OF SHORT‐TERM CULTURE ON POPULATIONS OF HEMOPOIETIC PROGENITOR CELLS FROM MOUSE MARROW
Authors: McCulloch E. A. , Till J. E.
Published: May 2008

We have studied the response of progenitor cells in mouse marrow to short‐term cultivation in cell culture. In the presence of a feeder layer of mouse renal tubules, the number of granulocyte progenitors able to form colonies in cell culture showed a net increase. No such increase in numbers of stem cells detected by the spleen colony assay was observed under the same conditions, although there was some stimulation of uptake of tritiated thymidine into these cells. A rapid decrease in the numbers of both types of progenitor cells occurred in the cultures in the absence of a feeder layer. However, when marrow cell populations that had been cultivated for 2 days in the absence of a feeder layer were transplanted into irradiated mice, the surviving stem cells detected by the in vivo assay showed a prolonged phase of rapid growth, resulting in a more pronounced ‘overshoot’ in the growth curve.
CARTILAGE CELL PROLIFERATION IN THE TAIL‐VERTEBRAE of NEW‐BORN RATS
Authors: Dixon B.
Published: May 2008

Cartilage cell proliferation has been studied in the tail‐vertebrae of new‐born rats. At 1 day the median cycle time for cartilage cells was about 22 hr; G1+ 1/2M, S, and G2+ 1/2M being 6.8 ± 2.5, 11.6 ± 2.2, and 4.6 ± 2.0 hr respectively. At 7‐10 days, cell proliferation is confined mainly to the lower half of the epiphysis. Here cycle times are longer, about 3 1/2 days in the most active region. Differences in cycle times appear to be due to either a lengthening of G1 or the entry of cells into a resting state. Changes in cartilage cell kinetics are discussed in relation to the structure and function of the epiphysis.
THE RELATIONSHIP BETWEEN CELL MATURATION and PROLIFERATION IN the ERYTHROID SYSTEM of the RAT
Authors: Hanna I. R. A. , Tarbutt R. G.
Published: May 2008

Calculations have been made of the change with time in the tritiated thymidine labelling index of erythroid cells in normal and anaemic rats, on the basis of two different models of the erythroid system. In the first model it is assumed that cells pass from one stage of maturation to the next at all phases of the cell cycle, whereas in the second model the cells can only progress to the next stage when they reach a certain point in the cell cycle. the changes in labelling index predicted on the basis of these two models are markedly different, especially in the non‐dividing stages of the system, and the change in labelling index as a function of time therefore provides an experimental method for distinguishing between the two models. the experimental data favours the model in which cells cross compartmental boundaries at all stages of maturation. Some important consequences of this model are discussed.
THE INFLUENCE of A LOW ENVIRONMENTAL TEMPERATURE ON the STEM CELL POPULATION of the BONE MARROW and INTESTINAL MUCOSA
Authors: Baker D. G. , Carsten A. L. , Hopper A. F.
Published: May 2008

Protracted exposure of rats to a low environmental temperature (2° C) resulted in almost a two‐fold increase in the number of colony forming units per femur. Following a dose of Vinblastine, return of CFUs in the bone marrow to the pretreatment level was more rapid in the cold exposed rats than in rats at a 25° C environment. the cell cycle time of the cells in the intestinal crypt was reduced for the cold exposed rats. These observations are thought to be the basis for the increased radioresistance and/or more rapid recovery from whole body irradiation previously reported.
ANOMALOUS STIMULATION OF PROTEIN SYNTHESIS: EVIDENCE FOR TRANSLATIONAL CONTROL IN PRIMARY CELLS
Authors: Christopher C. W. , Ishikawa Kiichi , Amos Harold
Published: May 2008

Chick cells in primary culture synthesize protein at an accelerated rate following recovery from prolonged (2‐12 hr) inhibition of protein synthesis. This ‘overshoot’ is followed by a return to the normal rate of synthesis.

Both actinomycin and fluorophenylalanine provided during the recovery period enhance the ‘overshoot’ and prevent the return to normal.

The results are consistent with the proposal that protein synthesis is restricted by an inhibitor or ‘governor’, itself a protein of relatively short half life.

Neither L nor HeLa cells demonstrate an ‘overshoot’ during the recovery phase.
THE TECHNIQUE OF LABELLED MITOSES: ANALYSIS BY AUTOMATIC CURVE‐FITTING
Authors: Steel G. G. , Hanes S.
Published: May 2008

An improved method is described for the analysis of data obtained by the technique of labelled mitoses. It is a development of the method described by Barrett (1966) in which theoretical curves are computed on the basis of a model which assumes that the phases G1, S and G2 are described by independent log‐normal distributions; the analysis consists in finding a form of this model which gives a labelled mitoses curve which is the best fit to the available data. This fitting procedure has now been made automatic. No comprehensive indication of the goodness of fit can be given, although in the analysis of over fifty sets of data the method appears to have worked well.

A supplementary computer program is described which, on the basis of three separate assumed modes of cell loss, calculates the form of the age distributions and theoretical continuous labelling curves. This allows growth fraction to be calculated in a way which takes account of the distribution of phase durations and the non‐rectangular age distributions of expanding cell populations. It also gives an opportunity to study the implications of continuous labelling data as regards the mode of cell loss.

A comparison is made between the present method of labelled mitoses curve analysis and the empirical rules which have often been used.
KINETICS OF THE INNER ENAMEL EPITHELIUM IN THE ADULT RAT INCISOR
Authors: Zajicek Gershom , Bar‐Lev Moshe
Published: May 2008

The inner enamel epithelium (IEE) in the model consists of a 1500 cell matrix. Cells formed on the apical side of the matrix proliferate and migrate towards its incisal (or distal) end, where they are shed. the continuous cell supply is maintained by two types of cell: (a) the blasts, which preserve their physical position in the matrix. Upon division, the blast yields one blast, occupying the space of the mother cell, and a migrating metablast. (b) the metablasts, which divide while migrating along the matrix. Each blast division forms a metablast clone whose size depends on the number of divisions its members undergo. the metablasts finally mature and cease to divide.

Each cell is described by three attributes which change with time: age, label content and the number of divisions it underwent since the metablast clone was formed. (This attribute is set to zero in the blasts.)

The system is governed by the following parameters: (a) the size of the blast compartment. (b) the number of divisions a metablast clone undergoes in its life time. (c) the lengths of the phases in the cell cycle. (d) the length of the time unit. (e) Degree of variation in the system (noise).

In the experiments described only one set of parameters was used: tc= 22 hr, tG1= 12.5 hr, ts= 7 hr, tG2= 2 hr, tm= 30 min, variation = 20%.

The model mimics well experimental results reported before, such as the migration rate of labelled cells on the IEE axis and labelled mitosis curve. It predicts new facts like changes in the grain count and labelled cell index with time.
NATURAL VARIATION IN THE S‐PHASE OF RENEWING EPITHELIA OF THE POUCHLESS OPOSSUM, MARMOSA MITIS
Authors: Thrasher J. D. , Berg N. B. , Hauber E.
Published: May 2008

The sites of cell proliferation and the duration of the S‐phases in epithelia (tongue, stomach, duodenum, jejunum, ileum and descending colon) of the pouchless opossum, Marmosamitis, have been studied following the injection of tritiated thymidine. the sites of cell proliferation in these epithelia are not significantly different than those reported for rodent tissues. On the other hand, measurements of the mean duration of DNA synthesis revealed great variability in this phase: tongue (12.8 hr), stomach (>14.0 hr), duodenum (8.5 hr), jejunum (8.6 hr), ileum (9.7 hr) and descending colon (11‐3 hr). In addition, the values obtained for the mean duration of t2 (G2+2/1M) are fairly constant among the various epithelia. It is concluded that the times obtained for the average duration of the S‐phases are longer and more variable in M. mitis than similar observations reported on renewing epithelia of eutherian mammals.
THE RELATIONSHIP BETWEEN SPLEEN COLONY PRODUCTION AND SPLEEN CELLULARITY
Authors: Lord B. I.
Published: May 2008

The fraction, f, of injected spleen colony‐forming cells which can be recovered from the spleen of a radiated mouse has been determined at various times up to 24 hr following the initial cell injection. the cellularity of the spleen at the time of assay was also measured and compared with the calculated f number. the linear relationship between these two parameters indicated that over the period of 2‐24 hr the number of CFU/106 spleen cells was constant, both falling in a parallel fashion. A further experiment using non‐irradiated W/Wv mice in which the spleen size did not change showed the same f number at the end of this period as at 2 hr. It is concluded that CFU are expelled from the spleen during its post‐irradiation contraction thus leading to the apparent fall in f number. It is also concluded that a more realistic f number is obtained by assaying the splenic CFU content 24 hr after the primary cell transfer rather than 2 hr.
PROLIFERATION KINETICS IN EPITHELIUM OF GUINEA‐PIG COLON
Authors: Sawicki W. , Rowiński J. , Blaton Olena
Published: May 2008

The distribution of mitotic, DNA synthesizing and mature goblet cells along crypts of different length, situated in various regions of the colonic wall circumference, was determined. the distribution of proliferating cells can be approximated by a normal curve, and the distribution of mature goblet cells by an exponential curve. Some of the parameters of the distributions, different for various crypt classes, are shown to have common values when normalized by dividing them by the crypt length in a given class. the results are considered as indicating the manifestation of two levels of control of proliferation: one establishing the common pattern of the distributions along different crypts, and the second causing the differences in distributions depending on the region of the colonic wall.
INCORPORATION OF TRITIATED THYMIDINE INTO THE SKIN AND HAIR FOLLICLES
Authors: Potten Christopher S. , Jessup Barbara A. , Croxson Mary B.
Published: May 2008

The incorporation of tritiated thymidine into the skin has been studied after the initiation of new hair growth by plucking. Techniques are described whereby the incorporation into hair follicles and into the basal layer of the epidermis can be studied independently. Fluctuations are observed in the levels of incorporation in both cell populations through the hair growth cycle. These fluctuations show great regularity. the early fluctuations have been attributed to synchronous progression of cells through the cell division cycle. the significance of the fluctuations is discussed with particular reference to (I) possible persistence of cell cycle synchrony, (II) regulatory feedback mechanisms controlling DNA synthesis, perhaps through specific mitotic inhibitors, (III) the existence of Go, G1 and G2 cell sub‐populations.
A QUANTITATIVE STUDY OF THE MITOTIC ACTIVITY IN THE SUBEPENDYMAL PLATE OF ADULT RATS
Authors: Hopewell J. W.
Published: May 2008

A quantitative study of the mitotic activity of the cells of the subependymal layer in the rat brain has shown that mitotic activity decreases with the increase in age of the animals. Mitotic activity is still found in rats 16 months old and in the case of animals of two strains of rats, of this age, the mitotic count is significantly higher in males than in females.

The relationship between a reduced rate of brain growth and the decline in mitotic activity and the significance and importance of the higher mitotic count in the subependymal plate of 16‐month‐old males compared with similar females is discussed.
THE APPLICATION OF AGE RESPONSE FUNCTIONS TO THE OPTIMIZATION OF TREATMENT SCHEDULES
Authors: Steward Palmer G. , Hahn George M.
Published: May 2008

A computer‐based technique is described for calculating the survival of normal and malignant cell populations during and after chemotherapy or radiotherapy. For exponentially growing cells, cell sensitivity as a function of the position in the cell cycle (age response function) is considered and survival calculated by means of a method discussed previously (Hahn, 1966; Hahn & Kallman, 1967). It is shown how the age response function is obtained from experimental data. Two examples of the application of the computer‐based technique are given. As one example, the technique is used to ‘optimize’ the scheduling of fractionated irradiations to differentially kill one cell line over another using as a basis for optimization differences in their age response functions. the second example illustrates the use of the technique to determine the relative advantage of different chemotherapy protocols. Here the survival of cycling and noncycling bone marrow stem cells, and resistant and sensitive malignant cells, is calculated. It is suggested that the technique may have direct relevance for the chemotherapy of some leukemias.
THE VALIDITY OF AUTORADIOGRAPHIC LABELING
Authors: Moffatt D. J. , Youngberg S. P. , Metcalf W. K.
Published: May 2008

As part of an experimental evaluation of autoradiographs after administration of 3H‐thymidine to rats, we estimated the background distribution of silver grains. the mean level was within normally accepted limits. the distribution of non‐isotope induced grains was such that the validity of all labeling studies which do not evaluate background must be subject to question.
PERIODICITY OF DNA SYNTHETIC ENZYMES DURING THE HeLa CELL CYCLE
Authors: Brent T. P.
Published: May 2008

The levels of the deoxynucleoside phosphokinases have been determined during the cell cycle in synchronous cultures of HeLa cells. Deoxycytidine and thymidine phosphokinases showed temporally similar periodic fluctuations while the purine deoxynucleoside phosphokinases showed a constant high activity. Experiments with metabolic inhibitors suggest that the observed rise in thymidine phosphokinase activity is directly due to the enzyme's biosynthesis.
EXCLUSION OF SERUM FACTORS IN THE IN‐VITRO DEPRESSION OF LYMPHOCYTES’ RESPONSE TO MITOGENS IN CHRONIC LYMPHOCYTIC LEUKAEMIA
Authors: Pentycross Christopher R.
Published: May 2008

To find out whether serum factors are involved in the depression of the mitogenic response of lymphocytes of patients with chronic lymphocytic leukaemia, sera from these patients were used in the culture medium for normal lymphocytes. the results were considered on the basis of the dynamics of responses of these normal lymphocytes, comparing a standard human group AB serum with twenty sera from patients with CLL. No heat‐stable inhibitory factors peculiar to CLL were found. In an experiment in which fresh CLL and normal sera were compared, no heat‐labile inhibitory factors were apparent.
THE SPERMATOGONIAL STEM CELL POPULATION IN ADULT RATS
Authors: Huckins Claire
Published: May 2008

Radioautographs of histological sections and whole mounted seminiferous tubules from adult rat testes were used to investigate the kinetic properties of the undifferentiated type A spermatogonial population (1) immediately following multiple injections of 3H‐TdR and (2) at long intervals after single or repeated injections.

Most of the undifferentiated type A cells became labeled by five or six successive injections of 3H‐TdR given at 12 hr intervals. Labeling frequency was greater than 90% in stages X‐I, and was maximal in stage I (96‐97%) where only a small proportion (15%) of the isolated undifferentiated spermatogonia (the As stem cells) failed to incorporate the label. Since this unlabeled cohort represented only 1‐3% of the total undifferentiated type A population in stages I‐VII, the existence of a large non‐cycling A0 or reserve stem cell population (which formed 21% of the total A population in stages II‐VII according to Clermont & Bustos‐Obregon, 1968) could not be confirmed. the non‐labeling of a few isolated stem cells was consistent with the previous finding of a prolonged G2 in some of these spermatogonia (Huckins, 1971c). It was therefore concluded that all undifferentiated A spermatogonia, including the As stem cells, were in active cell cycle.

Some well‐labeled isolated stem cells persisted for long periods and were still common 13 days (one cycle of the seminiferous epithelium) after 3H‐TdR injection. These appeared to be slow cycling elements which did not divide at all or possibly just once during this interval, but thereafter became mitotically active, giving rise to labeled pairs which in further divisions formed lightly labeled chains of aligned undifferentiated cells. There was a gradual disappearance of the labeled cells, so that by 26 days after 3H‐TdR injection no labeled A spermatogonia remained in the seminiferous epithelium.
MECHANISM OF EOSINOPHILIA
Authors: Spry Christopher J. F.
Published: May 2008

The kinetics of non‐dividing eosinophils was studied in normal rats and rats in which an eosinophilia had been induced by injecting Trichinella spiralis larvae intravenously. the findings suggested that in normal rats eosinophils matured in the spleen after leaving the marrow. the emergence time of eosinophils in normal rats was 41 hr, and was reduced in stimulated rats to 18 hr. Neutrophil emergence time was not reduced, indicating that there are separate mechanisms for regulating the rates of emergence of newly formed eosinophils and neutrophils.

The half‐life of eosinophils in the blood of normal rats was 6.7 hr, and was not altered 1.5–3.5 days after larvae were injected, when many eosinophils were accumulating in tissues. the rate of disappearance of labelled eosinophils from the blood was exponential, indicating random loss from the circulation. Eosinophils were mobilized into the pool of circulating eosinophils by a soluble plasma factor (‘eosinophil releasing factor’) which increased the number of circulating eosinophils at 3 and 6 hr. These experiments showed that the number of eosinophils in the blood was regulated by several different mechanisms, which were distinct from those affecting eosinophil production.
DNA SYNTHESIS TIME IN LEUKAEMIC CELLS AS MEASURED BY THE DOUBLE LABELLING AND THE PERCENTAGE LABELLED MITOSES METHODS
Authors: Harriss Eileen B. , Hoelzer D.
Published: May 2008

Values of Ts provided by the double labelling method have been compared with those given by the percentage labelled mitoses curve for blast cells in the peripheral blood of a patient with plasma cell leukaemia and of rats bearing a transferable acute leukaemia. the double labelling method was carried out giving the first label (3H‐thymidine) in vivo and the second label (14C‐thymidine) in vitro with several values for the interval between the two labels. Ts was calculated by fitting regression lines to the results obtained. Data for percentage labelled mitoses were analysed by computer. For the plasma cell leukaemia values of Ts= 17.1 ± 7.0 hr and Ts= 19.8 ± 3.4 hr, and for the rat leukaemia values of 8.7 ± 1.7 hr and 9.0 ± 1.7 hr (7.1 hr corrected for exponential growth) were obtained from the percentage labelled mitoses and double labelling methods respectively. It is concluded that the double labelling method is valid for the study of cell proliferation in leukaemic blast cells.
SHORT‐TERM CULTURES OF MOUSE MARROW CELLS SEPARATED BY VELOCITY SEDIMENTATION
Authors: Sutherland D. J. A. , Till J. E. , McCulloch E. A.
Published: May 2008

Our experiments were designed to identify the source of the increased number of cells forming colonies in culture (CFU‐C) detected after short‐term culture of mouse marrow cells over ‘feeders’ of renal tubules. Accordingly, marrow cell suspensions were fractionated by velocity sedimentation and aliquots of each fraction cultured for 2 days over tubule ‘feeders’. We found a greater increase of CFU‐C in suspensions of slowly sedimenting cells as compared to rapidly sedimenting cells. Colcemid and vinblastine were used to alter the peak sedimentation velocity of marrow suspensions by changing the distribution of cells in the cell cycle. After such manipulations, the peak increase in CFU‐C continued to be associated with fractions containing slowly sedimenting cells. Such fractions also contained most of the pluripotent stem cells identified by the spleen colony technique.