bluuebunny/crossref_metadata_2025 huggingface dataset:
GROWTH AND CELL POPULATION KINETICS OF SINGLE AND MULTIPLE KHT SARCOMAS
Authors: Rockwell Sara , Kallman Robert F.
Published: May 2008

KHT sarcomas were implanted in syngeneic C3H/Km mice either as single intradermal tumors on the flank or as nine or ten intradermal tumors on the back. The growth curves of the single and multiple tumors were indistinguishable throughout the accurately measurable volume range. The cell population kinetics of the single and multiple tumors, examined by the per cent labeled mitoses technique, were not significantly different in any respect. The cell population kinetics in the center and periphery of the single tumors were examined separately and found to be the same.
THE EFFECT OF CHEMOTHERAPY ON THE GROWTH OF LEUKEMIA L1210 II. PERSISTENCE OF A NITROSOUREA‐INDUCED CHANGE IN THE GROWTH CHARACTERISTICS OF TRANSPLANT GENERATIONS
Authors: DeVita Vincent T. , Bray David A. , Bostick Frieda , Bagley Charles M.
Published: May 2008

A strain of murine leukemia L1210 was treated with subcurative doses of 1,3 bis‐(2‐chloroethyl)‐1‐nitrosourea. When the leukemia cells repopulated the abdominal cavity, aliquots were transplanted to other animals and the growth characteristics measured.

A PLM curve obtained twenty‐one generations later had a different configuration than the control line with a prolongation of Ts and Tc. The configuration suggested that treatment with BCNU may have led to the selective growth of a population of cells with a longer Tc and less variation about the mean Tc. Permanent actual alteration of Tc could not be excluded. Measurements of TD also appeared to be affected by the number of tumor cells present on the day of the study. Although Tc was prolonged in drug‐exposed transplanted cell lines, cell loss, which may be influenced by many factors, appears to be the major factor that must be considered in alterations of doubling times in this model tumor system.
FOETAL ERYTHROPOIESIS IN GENETICALLY ANAEMIC, FLEXED‐TAILED (f/f) MICE
Authors: Tarbutt R. G. , Cole R. J.
Published: May 2008

This paper presents measurements of foetal weights, haemoglobin concentrations, red cell counts, blood volumes, erythroblast thymidine labelling indices and cell cycle parameters in genetically anaemic, flexed‐tailed (f/f) and haematologically normal (f/+) foetuses.

The production of red blood cells from the livers of (f/f) foetal mice lags behind that of heterozygote (f/+) foetuses, and the cells that are produced are small and poorly haemoglobinized. The anaemia is not due to an abnormal cell cycle in f/f erythroblasts, which appear to be capable of responding to the anaemia by a small increase in their rates of proliferation. The number of red cells in the foetal circulation can be calculated from the cell cycle time and number of hepatic erythroblasts; the calculated number agrees quite well with the measured number in both f/f and f/+ foetuses. Many characteristics of the anaemia of the f/f foetus can be accounted for if it is assumed that there is a deficiency in the production or activity of an enzyme involved early in the haem synthetic pathway.
AUTORADIOGRAPHIC INVESTIGATION ON THE CELL KINETICS OF CRYPT EPITHELIA IN THE JEJUNUM OF THE MOUSE °CONFIRMATION OF STEADY STATE GROWTH WITH CONSTANT FREQUENCY DISTRIBUTION OF CELLS THROUGHOUT THE CYCLE
Authors: Schultze B. , Haack V. , Schmeer A. C. , Maurer W.
Published: May 2008

Cell kinetic parameters of cells in the crypt of the jejunum of the mouse were obtained autoradiographically. A number of different methods used in cell proliferation studies were applied to the same animal strain kept under constant conditions. In order to avoid effects of geometrical factors, squashes of isolated crypts were used.

The generation time was determined by the per cent labelled mitoses method of Quastler, modified by double labelling with 3H‐ and 14C‐TdR. This modified method permits a more exact determination of the generation time. The duration of the cycle was 14 hr.

Double labelling experiments in which an injection of 3H‐TdR was followed by an injection of 14C‐TdR after 1 hr showed that the cell flux was 7.0%/hr at the beginning of the S‐phase and 7.68%/hr at the end. Assuming steady state growth a constant cell flux of 7.15%/hr within the whole cycle can be derived from the measured generation time of 14 hr. These results clearly show that the crypt epithelia constitute a steady state system with constant frequency distribution of the cells throughout the cycle.

The per cent labelled mitoses method after a single injection of 3H‐TdR as well as double labelling experiments with 3H‐ and 14C‐TdR give an estimate of the S‐phase of 8.0 or 7.4 hr respectively. Double determinations lead to a value of 0.54 or 0.52 hr respectively for the duration of mitosis and to values of 77% and 72%
THE PROLIFERATIVE CAPACITY OF HAEMOPOIETIC COLONY FORMING UNITS IN THE RAT
Authors: Dunn C. D. R.
Published: May 2008

After transplantation into rats lethally treated with cytotoxic chemicals both bone marrow and spleen CFU in the spleen and spleen derived CFU in the bone marrow expand with doubling times (Td) of approximately 18 hr. However, bone marrow derived CFU in the bone marrow have a Td of 36 hr. Evidence obtained using tritiated thymidine in vitro and methotrexate in vivo show that the proliferation rate of bone marrow derived CFU is similar in both the bone marrow and spleen and calculations suggest that the different Td between these two sites is due to the higher loss of CFU through differentiation in the bone marrow compared to the spleen. These findings further support the hypothesis of an environment in the spleen which favours CFU self‐maintenance over differentiation with the opposite situation occurring in the bone marrow.
AN ESTIMATION OF PROLIFERATIVE POPULATION SIZE IN STOMACH, JEJUNUM AND COLON OF DBA‐2 MICE
Authors: Kovacs Laszlo , Potten Christopher S.
Published: May 2008

Liquid scintillation and autoradiographic techniques have been used to provide quantitative data on the proliferative units, the crypts, of stomach, jejunum and colon of DBA‐2 mice. A slight modification of the crypt squash technique has provided data suggesting that about 50% of the cells of the jejunal crypt are at any given time in the proliferative state. This value is lower in the colon while in the stomach glands only 20% of the cells are involved in cell production. The data provide estimates for cell cycle times of 26·3, 16·0 and 23·2 hr for stomach, jejunum and colon respectively.

The size and number of proliferative units have been determined for three regions of the gastrointestinal tract of mice. A review of the literature suggests that considerable strain differences may exist.
PROPERTIES OF HAEMOPOIETIC STEM CELLS IN PHENYLHYDRAZINE TREATED MICE
Authors: Hodgson G. S.
Published: May 2008

Recovery of erythropoiesis was fast in Balb/c mice irradiated 700 R 5 days after initiation of phenylhydrazine treatment and took place predominantly in the spleen, which showed numerous large frequently confluent endogenous colonies. Post irradiation phenylhydrazine induced anaemia did not accelerate recovery of erythropoiesis; it did, however, produce a slight but significant rise in endogenous colony formation.

Radiosensitivity of spleen CFU‐S from phenylhydrazine treated mice was similar to that of CFU‐S in normal mouse spleen.

Spleen CFU‐S in mice 5 days after initiation of phenylhydrazine treatment were sensitive to the lethal action of Hydroxyurea, while bone marrow CFU‐S were not.

The self‐renewal capacity of CFU‐S in the endogenously repopulated spleen of phenylhydrazine pretreated 700 R X‐irradiated mice was low when compared to that of spleen exogenously repopulated by cells from normal mouse bone marrow, normal and phenylhydrazine treated mouse spleen. CFU circulating in blood of phenylhydrazine treated mice had a low self‐renewal capacity.

The marked strain differences in self‐renewal capacity of spleen CFU‐S, and of the capacity of spleen CFU‐S to increase by proliferation are discussed.
CONTROL OF EPITHELIAL CELL PROLIFERATION IN THE SMALL INTESTINAL CRYPT
Authors: Tutton P. J. M.
Published: May 2008

A heat labile factor which has been shown to inhibit proliferative activity in crypt epithelium both in rat jejunum in vivo and in explants of rat jejunum maintained in organ culture has been prepared from the soluble fraction of homogenized epithelial cells isolated from rat small intestinal crypts. The factor appears to have tissue specificity, for it has no influence on epithelial cell proliferation in colonic crypts, oesophagus or skin. Extracts of rat intestinal villous cells prepared using identical techniques were without effect on proliferative activity of small intestinal crypt epithelium.

Isoprenalin, which was also found to suppress cell proliferation, did not potentiate the effect of the factor and its effects were evanescent.
IN VITRO AND IN VIVO LABELLING OF ANIMAL TUMOURS WITH TRITIATED THYMIDINE
Authors: Denekamp Juliana , Kallman R. F.
Published: May 2008

The labelling indices obtained by incubating tumour specimens with tritiated thymidine in vitro under hyperbaric oxygen have been compared with those obtained by labelling a matched tumour in vivo. The correspondence between these individual labelling indices is sometimes very poor; however, the average labelling index derived from groups of tumours labelled in the two ways does not differ significantly. There was a large variation from field to field within any tumour, and considerable variation from one tumour to another within each tumour type. The mitotic index was also compared in the matched tumour preparations; the mitotic index in vitro was almost always considerably lower than the values observed in vivo.
AUTORADIOGRAPHIC CONFIRMATION OF THE MITOTIC DIVISION OF EVERY MOUSE JEJUNAL CRYPT CELL LABELLED WITH 3H‐THYMIDINE
Authors: Burholt D. R. , Schultze B. , Maurer W.
Published: May 2008

The question was investigated of whether for crypt epithelia of the jejunum of the mouse all cells labelled after a single injection of 3H‐TdR subsequently divide or whether cells exist in the crypt which synthesize metabolic DNA and, therefore, do not undergo division after labelling.

A double labelling experiment was performed with a first injection of 3H‐TdR followed 1 hr later by an injection of 14C‐TdR. Then from double emulsion autoradiographs of isolated squashed crypts the number of 3H‐only, 14C‐only and double labelled cells and mitoses were counted.

The double labelling produced a narrow, 1 hr wide sub‐population of 3H‐only labelled cells. This subpopulation of S cells completed its division before labelled cells were lost from the crypts by migration onto the villi. The results showed that this subpopulation of 3H‐only cells completely doubled within 3 hr and then remained constant through 6 hr. From this result it was concluded that every cell labelled after a single injection of 3H‐TdR divides.

From the same autoradiographs the flow rate through the end of mitosis was measured. From the flow rate and the mitotic index a mitotic duration of 0·5 hr was determined. The agreement of this measured mitotic time with the value calculated from the labelling index, mitotic index and S duration is also strong evidence that every labelled cell divides.

Both experiments show that the intestinal crypt does not contain cells synthesizing metabolic DNA.
ACTION OF HYDROXYUREA AND N‐CARBAMOYLOXYUREA ON THE CELL CYCLE OF TETRAHYMENA
Authors: Cameron I. L. , Jeter J. R.
Published: May 2008

Addition of a 50 mm dosage of hydroxyurea (HU) to growing cultures of the cilitate Tetrahymena pyriformis allows cell growth to continue but inhibits DNA synthesis, and inhibits cell division after a 20–30% increase in cell number. Higher concentrations of HU cause cell death. T. pyriformis strain differences exist in sensitivity to HU. No cytotoxicity selective to a specific phase of the cell cycle could be demonstrated.

The inhibitory effects of HU are entirely reversed by removal of HU and this procedure can be used to induce cell cycle synchrony. Supplementing HU treated cells with deoxyribonucleosides relieves the inhibitory action of HU.

Carbamoyloxyurea (COU) is a reactive intermediate of HU and its action on Tetrahymena appears to be similar to that of HU. Because of this similarity and because COU is more potent than HU we postulate that COU is responsible for the unique properties previously ascribed to HU.
TEMPERATURE EFFECTS ON THE KINETICS OF SPERMATOGENESIS IN THE MOUSE
Authors: Meistrich M. L. , Eng V. W. S. , Loir M.
Published: May 2008

The kinetics of spermatocyte differentiation in adult mice was measured under normal conditions, during maintenance at elevated temperatures and following experimental cryptorchidism. For these measurements the development of 3H‐TdR labelled testis cells was followed by velocity sedimentation at unit gravity and the results were in agreement with those obtained by autoradiography. In the cryptorchid animals and those maintained at 32°C the kinetics of spermatogenesis during treatment was increased by at least 13% over control values. Smaller but significant increases in the kinetics of spermatogenesis were obtained at ambient temperatures of 28 and 30°C without any observable histological damage. The increased kinetics is believed to be a direct effect of temperature on testis cell development.
THE NORMAL TRANSPLACENTAL PASSAGE OF MATERNAL RED CELLS IN MICE
Authors: Holliday Jean , Barnes R. D.
Published: May 2008

51Cr labelled red cells injected into pregnant mice were subsequently detected in peripheral blood of their progeny when examined in autoradiography. The fact that these labelled cells were seen in the offspring from five different strains of mice suggests that this transplacental passage is probably a ‘normal’ phenomenon.
ANALYSIS OF PROLIFERATION AND DIFFERENTIATION OF FOETAL GRANULOCYTE‐MACROPHAGE PROGENITOR CELLS IN HAEMOPOIETIC TISSUE*
Authors: Moore M. A. S. , Williams N.
Published: May 2008

Analysis of in vitro colony formation in agar cultures of foetal haemopoietic tissues of eight mammalian species has shown that granulocyte‐macrophage progenitor cells are present in foetal liver, yolk sac, marrow and spleen in numbers approaching the incidence in adult marrow. Such characteristics as buoyant density, growth rate and differentiation served to distinguish foetal from adult colony forming cells (CFCs).

Cell cycle analysis performed by exposing haemopoietic cells to high doses of tritiated thymidine in vitro showed that foetal CFC proliferation in species of short gestation (rabbit, rat, mouse) approached or exceeded that observed in adult marrow. In contrast, in species of long gestation (human, monkey, calf, lamb, guinea‐pig) a period of variable duration was observed when foetal liver CFCs entered a non‐cycling G0 or blocked G1 phase. In these species foetal liver CFCs were found to be proliferating actively early in gestation and following the non‐cycling phase again re‐entered a proliferative state associated with onset of active granulopoiesis in foetal marrow and possible migration of CFC from liver to marrow.

These results indicate the existence of granulocyte‐macrophage progenitor populations displaying foetal characteristics and adapted to particular stages of haemopoietic development, a situation which closely parallels that reported for erythropoiesis.
PROLIFERATION OF LIVER EPITHELIA IN THREE‐WEEK‐OLD RATS
Authors: Schultze B. , Maurer W.
Published: May 2008

The proliferative activity of liver epithelia in 3‐week‐old rats was studied auto‐radiographically using 3H‐thymidine. Only a single peak of labelled mitoses (late pro‐ to anaphases) at 7 hr was found in the per cent labelled mitoses curve after injection of 3H‐thymidine. A second peak at about 32 hr described by Post, Huang & Hoffman (1963) and Post & Hoffman (1964, 1965) as well as Grisham (1969) and a cycle time of about 22 hr derived from the distance between the two peaks could not be confirmed by the present work.

According to the present experiments the cycle time of parenchymal liver cells in 3‐week‐old rats must range between 50 hr (with a growth fraction of 0·25) and 7·1 days (with a growth fraction of 1·0). The present results do not support the existence of a growth fraction of only 0·1 as assumed by Post et al. (1963).
PROLIFERATION KINETICS OF SHAY CHLOROLEUKAEMIA CELLS GROWN IN DIFFUSION CHAMBERS IN VIVO
Authors: Vilpo J. A. , Rytömaa T.
Published: May 2008

The proliferation kinetics of Shay chloroleukaemia cells was studied by the labelled mitoses technique and some other methods. Detailed estimates of the phase durations of the cell cycle for proliferating cells were obtained using young, exponentially growing diffusion chamber cultures; estimates of kinetic parameters were also obtained for ‘old’ cultures and for local subcutaneous chloroma tumours. The results enabled determination of the growth fraction and the cell loss factor.

Cell loss was found to be the dominant factor determining the growth rate of chloroleukaemia cell populations. The mechanism of cell loss was cell death. Some implications of these findings are discussed.
PREVENTION OF GRAFT VERSUS HOST REACTION BY INCUBATION OF LYMPHOID CELLS WITH A SPLENIC EXTRACT (NOT AFFECTING THE REPOPULATION OF THE HAEMOPOIETIC TISSUE)
Authors: Garcia‐Giralt E. , Morales V. H. , Bizzini B. , Lasalvia E.
Published: May 2008

An alcohol extract of calf spleen possessing the in vivo characteristics of a lymphoid chalone has already been shown to prevent or to control the acute graft versus host reaction (GVHR) in lethally irradiated F1 recipients, when given respectively to the parental cell donors or to the F1 recipients. The present experiments demonstrate the efficacy of the incubation of the donor cells with this extract on the prevention of GVHR, and shows that it selectively inactivates cells responsible for it.
GRANULOPOIESIS AND CELL KINETICS IN CHRONIC MYELOID LEUKAEMIA
Authors: Gavosto F.
Published: May 2008

The present study is an analysis of the kinetic data for chronic myeloid leukaemia derived from personal observations and cases reported in the literature. A comparison is made with the parameters for normal granulopoiesis and the growth pattern of the CML cell population discussed.
GROWTH OF STEM CELL CONCENTRATES IN DIFFUSION CHAMBERS (DC)
Authors: Quesenberry P. , Niskanen E. , Symann M. , Howard D. , Ryan M. , Halpern J. , Stohlman F.
Published: May 2008

The growth in diffusion chamber (DC) of normal murine marrow and marrow separated by discontinuous albumin centrifugation was studied. The colony‐forming cells (CFC) assayed in soft agar, total cell counts and differentials were measured in the DC over a 19 day period after intraperitoneal implantation into CF1 mice. Growth of implants of normal marrow or fraction 3 (F3) in which CFC had been concentrated 1.7–3.9‐fold were compared at an initial cell concentration of 1 × 105. There was a good correlation between the number of CFC implanted with granulocyte production but not with macrophage production. When higher cell concentrations of normal unfractionated marrow were implanted growth was reduced as was recovery of CFC. In two experiments in which both CFU and CFC concentrations were measured there was a general correlation between the two.
CELL KINETICS IN THE SEBACEOUS GLANDS OF THE MOUSE. II. THE GLANDS DURING HAIR GROWTH
Authors: Hamilton E. , Howard A. , Potten C. S.
Published: May 2008

The sebaceous glands of the mouse have been studied during hair growth initiated either spontaneously or artificially.

The labelling index of the glands increases early in the spontaneous hair growth period. That of the epidermis is much lower and hardly changes during the growth period.

After the initiation of hair growth by plucking, changes in cell proliferation in the sebaceous glands appear to follow those in the epidermis. The size of the gland and the number of cells in it also change after plucking. These variations can be related to the stages of hair growth.
FIBROBLAST CELL KINETICS IN THE PERIODONTAL LIGAMENT OF THE MOUSE
Authors: Zajicek Gershom
Published: May 2008

Twelve male mice were injected intraperitoneally with tritiated thymidine. Six were sacrificed after 1 hr and six after 7 days. The right manibular incisors were dissected, cut sagittally and dipped in liquid emulsion. In the exposed and stained slides, observation was restricted to the lingual side of the periodontal ligament. Cells were evaluated sagittally from the basal tooth end up to the distance of 5 mm and up to the depth of 100 μm in the direction of socket wall. Cell and grain count was evaluated separately in 100 × 10 μm rectangles, creating a two‐dimensional array onto which the periodontal ligament was mapped.

The progenitor compartment extends up to the distance of 2400 μm from origin. Fibroblasts leaving this compartment migrate at different velocities, creating a velocity profile across the ligament. Adjacent to the socket wall cell movement is sluggish, whereas the fastest cell movement is exhibited by cells located 20–30 μm from the tooth.

The existence of such a profile indicates a continuous renewal of intercellular bonds, consistent with a process of actively pulling the incisor from its socket by the migrating fibrocytes.
ARE CELL KINETIC DATA RELEVANT FOR THE DESIGN OF TUMOUR CHEMOTHERAPY SCHEDULES?*
Authors: Putten L. M. van
Published: May 2008

The data on the importance of the application of information on cell kinetics for the success of tumour chemotherapy are critically reviewed. It is concluded that the data on cell sensitivity to drugs as affected by cell kinetic variables are as yet insufficient to permit the prediction of optimal dosage schedules for tumour therapy. More information is needed on differential responses and differential kinetic features of normal and malignant tissues. Optimistic views of cell kinetics as an easy answer to the problems of drug dosage schedule design are unjustified, but so is the disenchantment with cell kinetics as a fruitful approach. Much further work, especially on the drug sensitivity of cellular compartments in slow growing tumours, is needed before a complete evaluation of this tool is possible.
CELL PRODUCTION IN TUMOUR ISOGRAFTS MEASURED USING VINCRISTINE AND COLCEMID
Authors: Smith S. Rolf , Thomas D. Brynmor , Riches A. C.
Published: May 2008

Vincristine sulphate has been found to be a more useful metaphase arrest agent than Colcemid. Metaphase accumulation, in isografts of a CBA mammary adenocarcinoma, was linear with time for at least 10 hr after vincristine administration and also independent of drug dose in the range 1–4 mg/kg body weight.

A method for evaluating the cell production rate, in histological sections, of a cell population which forms a heterogeneous component of the tissue has been described. The percentage of each tissue component was determined using the Chalkley point count method and the mean number of metaphases in an arbitrary defined field were evaluated. Corrections for percentage composition and sectioning were applied and the cell production rate defined. This was found to be 15.8 ± 0.6 cells per 1000 cells per hour for this tumour.
THE RECOVERY FROM VARIOUS GRADATIONS OF CELL LOSS IN THE MOUSE SEMINIFEROUS EPITHELIUM AND ITS IMPLICATIONS FOR THE SPERMATOGONIAL STEM CELL RENEWAL THEORY
Authors: Keulen C. J. G. van , Rooij D. G. de
Published: May 2008

The recovery of the seminiferous epithelium from cell loss has been investigated by counting the different kinds of A‐spermatogonia and resting primary spermatocytes in stages 7–8 of the cycle of the seminiferous epithelium at different intervals of time after injection of several dose levels of the alkylating agent Myleran.

It was found that the decrease in total number of A‐spermatogonia is directly related to the logarithm of the dose of Myleran given. After all doses used, the total number of A‐spermatogonia starts to increase again between day 8 and 10. During the first part of the recovery, between day 8 and 16, the number of morphologically undifferentiated A‐spermatogonia increases, its maximal value being linearly dependent on the logarithm of the dose of Myleran given.

Between day 24 and 32, the total number of A‐spermatogonia overshoots control values significantly only when large doses of Myleran are used, no overshoot having been observed at low doses. This suggests the existence of an all or none relationship between overshoot and cell loss. The number of resting primary spermatocytes never overshoots control values.

The results are discussed as to the information they might give on the numerical behaviour of the stem cells of spermatogenesis.
THE CELL CYCLE TIME IN THE RAT JEJUNAL MUCOSA
Authors: Al‐Dewachi Huthaifa S. , Wright Nicholas A. , Appleton David R. , Watson Alexander J.
Published: May 2008

The regional variation of the duration of cell cycle parameters was studied by constructing fraction of labelled mitoses curves at several levels in the jejunal crypt column of male Wistar rats. Prolonged Tc and Ts values were apparent only in the bottom eight cell positions, and these differences were shown to be significant compared with the remaining cell positions by analysing the data by the method of Gilbert (1972). Above cell position 8 the proliferating crypt cells showed effectively the same phase durations. For the whole crypt column Tc was 11.32 ± 0.14 (SE) and Ts 6.49 ± 0.10.

Although variation in phase durations was confined to the basal portion of the crypt, the results essentially confirm the findings of Cairnie, Lamerton & Steel (1965a), and may be interpreted in terms of the slow cut‐off model. The demonstration of prolonged Tc values in basal cell positions confirms the presence of a longer cycling subpopulation of cells at the bottom of the crypt.
THE INFLUENCE OF INJECTED TRITIATED THYMIDINE ON THE MITOTIC CIRCADIAN RHYTHM IN THE EPITHELIUM OF THE HAMSTER CHEEK POUCH*
Authors: Møller Ulla , Larsen Jorgen K. , Faber Mogens
Published: May 2008

The initial effect of an injection of TdR‐5‐3H (1 μCi/g body weight; 6 Ci/mmol) in the cheek pouch epithelium of the Syrian hamster is an increase in the mitotic index. The increase is observed 1–5 hr after injection, depending upon the time of day when the injection is given, and is followed by compensatory variations in mitotic index. This deviation from the normal circadian rhythm in the mitotic index appears to depend on the fraction of G2‐cells at the time of injection. The main effect is a shortening of tg2. No effect is observed after injection of non‐radioactive TdR or isotonic saline. The results of the present experiment emphasize that unexpected results may be obtained when using mitotic indices from animals labelled with 3H‐TdR, as well as the risks of using the PLM‐method in a partially synchronized system.
HAEMOPOIETIC STEM CELL (CFU) KINETICS IN THE CULTURE
Authors: Chertkov J. L. , Samoylina Nina L. , Rudneva Nina A. , Rakcheev A. M. , Kondratenko Nona F.
Published: May 2008

Haemopoiesis continued for over 2 months in organ culture of embryonal mouse liver, and haemopoietic stem cells (CFUs) capable of DNA‐synthesis were found in it all that time. Between the 10th and 40th day the number of stem cells in the culture was sustained in a steady state. Both in normal and in regenerating adult bone marrow haemopoiesis ceased within a short time in the culture. Induction of proliferation in haemopoietic stem cells combined with undamaged or improved micro‐environment resulted in a little better maintenance of CFUs in the adult bone marrow culture, The results are discussed in the light of current concepts of haemopoietic stem cell regulation.
CONTINUOUS LABELLING STUDIES ON MOUSE SKIN AND INTESTINE
Authors: Potten Christopher S. , Kovacs Laszlo , Hamilton Elizabeth
Published: May 2008

Data are presented for changes in absolute radioactivity levels and labelling indices (LI) in three tissues: jejunum, colon and dorsal skin in the mouse during conditions of repeated (every 3 hr for 168 hr) 3H‐TdR (5 μCi) injections. The lengths of S and the cell cycle were estimated. The crypt and mucosal transit times were evaluated. There is a slowly cycling subpopulation in the crypt which may be the goblet cell precursors or a crypt stem cell population. The skin LI data cannot be fitted by a single straight line and the procedure of continuously handling or injecting the animals appears to result in a disturbance of the steady state. The liquid scintillation data for all samples showed some consistent and surprisingly large fluctuations and a clear deviation from linear uptake with increasing time.
COMPENSATORY GROWTH IN THE RAT TIBIA
Authors: Dawson Anne , Kember N. F.
Published: May 2008

When the proximal cartilage plate of one tibia of a rat is sterilized by radiation, compensatory growth occurs at the distal plate of the same bone. This growth is marked by small changes in the cell kinetic parameters and histology of the growth cartilage when compared with the distal cartilage plate in the unirradiated tibia. The changes are consistent with a delay in the maturation of the plate showing compensatory growth. Some possible mechanisms are considered, but the evidence available at present does not give decisive support to any particular theory.
DYNAMICS OF LEUKOCYTE MIGRATION INTO THE MOUSE ASCITES TUMOR
Authors: Lala P.K.
Published: May 2008

There is a marked increase in the number of peritoneal leukocytes (lymphocytes, monocytes and granulocytes) during the growth of Ehrlich ascites tumor in mice. No local proliferation (as indicated by a labeling at 1 hr following a single 3H‐TdR injection) was observed in the normal peritoneal leukocytes or those in the ascites tumor, except for a very minor labeling of some tumor macrophages. Kinetics of peritoneal leukocytes was studied with a series of twelve injections of 3H‐thymidine (20 μCi every 8 hr) in normal mice as well as mice injected with 106 tumor cells i.p. 2 hr after the last 3H‐TdR injection. Animals were sacrificed at intervals up to 6 days. Granulocyte labeling in the blood as well as peritoneal space was near 100% in both groups of animals at all the intervals. Temporal changes in the labeling of lymphocytes (from 10% at 0 day to 22% at day 6), and monocytes (from 20% at 0 day to 57% at day 6) were identical in the blood and peritoneal space of normal animals, indicating a free exchange of cells between these compartments. Higher labeling indices than those in the controls were attained in the blood of tumor‐bearing hosts (viz 40% for lymphocytes and 80% for monocytes at 6 days) suggesting an increased turnover of these cells in the circulation. In addition, peritoneal mononuclear cells of tumor‐bearing mice showed even a higher labeling than those in the blood (viz 65% for lymphocytes and 92% for monocytes at 6 days) indicating a selective migration and/or retention of newly formed cells within the tumor, in contrast to a random migration into the normal peritoneal cavity. Furthermore, an identical labeling of macrophages to that of monocytes within the tumor indicated a short monocyte‐macrophage transition. The preferential accumulation of young mononuclear cells into the tumor may be of functional importance.
THE INFLUENCE OF GENETIC RESISTANCE ON CFU GROWTH KINETICS IN SPLEEN AND FEMUR
Authors: Buurman W. A. , Bruggen Ivonne VAN , Vos O.
Published: May 2008

An impaired colony formation of C57BL marrow cells transplanted into Ft (C57BL x CBA) mice was observed. In accordance with the literature this phenomenon has been designated as ‘genetic resistance’. Studies to elucidate the mechanism of the genetic resistance demonstrated that the multiplication phase of the CFU growth curve started in the semi‐isogeneic combination about 48 hr later than in the isogeneic combination. In the spleen this resulted in a lower ‘dip’. For the spleen as well as for the femur similar CFU doubling times were found during the multiplication phase when both transplantation combinations were compared. Furthermore the percentage of CFU in S‐phase (assessed with the 3H‐TdR suicide technique) during the first days after transplantation were similar in both combinations. When the spleen was removed 5–6 months before irradiation and bone marrow transplantation was performed the growth curve of parental CFU in the femur was identical with the growth curve of isogeneic CFU (no delay was observed). These results are discussed and a few theories explaining the observations are proposed.
CHANGES IN INTESTINAL CELL KINETICS IN THE SMALL INTESTINE OF LACTATING MICE
Authors: Harding J. D. , Cairnie A. B.
Published: May 2008

The enlargement of the small intestine of mice during lactation is due, at least in part, to hyperplasia in the mucosal crypts and villi. The number of cells per crypt increases by 130% and the cell production rate by 63% after 15 days of lactation. These parameters were measured from crypt squashes and sections using both double‐label and PLM techniques. Neither the numbers of crypts and villi in the small intestine nor the turnover time of post‐mitotic cells on the villi changed.

A number of factors appear to act in concert during lactation to trigger this increase in epithelial cell number in the small intestine. The experiments reported suggest a role for the increased quantity of food consumed by the lactating animal, for changing hormonal levels, and for the increased demands placed on the body by milk production.
A COMPARTMENTAL ANALYSIS OF CIRCULATORY LYMPHOCYTES IN THE SPLEEN
Authors: Hammond B. J.
Published: May 2008

A tentative model describing the passage of circulatory lymphocytes through the spleen is formulated in accord with known anatomical features. In order to preserve isomorphism between the model and the splenic system, the model is formulated in compartmental form and its design allows alternative routes and modes of lymphocyte transit to be considered. The simultaneous differential equations arising from the model are solved using an analogue computer which also provides the means whereby the performance of the model may be compared with suitable dynamic data drawn from literature. This not only allows the selection of a particular configuration of the model in preference to its alternatives, but also allows the numerical determination of certain unknown parameters. In the case of the rat spleen, best agreement between model and experimental data is obtained when between 10 and 25% of the total lymphocyte flux in the model spleen passes through the marginal zone where the average dwell time of the lymphocytes is about 50 min. The white pulp receives a lymphocyte flux from the marginal zone amounting to about 10% of the total splenic flux and the white pulp lymphocytes are sequestered for a period of 4–6 hr before release to the venous circulation. The red pulp receives 90% of the total splenic flux but the majority of lymphocytes find transit through the red pulp in less than 5 min. The remaining flux of lymphocytes, amounting to 10% of the splenic input, is delayed in transit through the red pulp by 2–3 hr before release to the venous circulation.
THE EFFECT OF ESTRADIOL ON THE CELL KINETICS IN THE UTERINE AND CERVICAL EPITHELIUM OF NEONATAL MICE
Authors: Eide Arne
Published: May 2008

The effect of estradiol‐17β on the length of the various phases of the cell cycle was studied in the neonatal mouse uterine, and cervical epithelium. A double labelling method was used, and in addition labelled mitoses were counted. In the uterus proper, estradiol shortens the length of the total cell cycle, Tc, from 17‐9 hr to 15‐7 hr, and the duration of S phase, Ts, from 6–7 to 5‐1 hr 6 hr after estradiol treatment. 12 hr after estradiol treatment, Tc is shortened to 7‐4 hr and Ts to 4–5 hr. The shortening of Tc at 12 hr is mainly due to an effect on TG1, which is shortened from 8–55 hr in untreated animals to 1–8 hr in estradiol treated animals.

The Tc of cervix epithelium cells in untreated animals was found to be 21‐8 hr. After treating the mice for 6 hr with estradiol the Tc was now increased to 47 hr and further to 61 ‐2 hr following 12 hr treatment with the hormone. Ts increases from 8‐3 hr to 15‐2 hr following 6 hr estradiol treatment, and to 15‐4 hr after 12 hr treatment. The effect is most pronounced in TG1, which is lengthened from 10–95 hr in untreated animals to 28‐1 hr and 43 hr, respectively, in animals treated for either 6 or 12 hr with estradiol.
THE EFFECT OF CONTINUOUS IRRADIATION ON CELL PROLIFERATION AND MATURATION IN SMALL INTESTINAL EPITHELIUM
Authors: Rijke R. P. C. , Plaisier H. , Hoogeveen A. T. , Lamerton L. F. , Galjaard H.
Published: May 2008

Autoradiographic studies and scintillation counting of crypt material after pulse labelling with 3H‐thymidine showed that during continuous irradiation with 290 rads/day a reduced proliferative activity is present in the crypts of rat small intestine after 1 day of irradiation and of normal activity during the remaining period (5 days) irradiation. After cessation of irradiation an increase in proliferative activity can be observed after 1 day of recovery. From the time (36–48 hr after starting of the irradiation) that the number of villus cells is reduced an expansion of the proliferation zone in the crypt was observed. Both effects last until 1 day of recovery after cessation of irradiation. The process of crypt cell maturation and of villus cell function has also been studied during and after continuous irradiation by micro‐chemical enzyme analyses in isolated crypts and villi. It was found that the expansion of the proliferation zone in the crypt is accompanied by a decrease in activity of only those enzymes (i.e. non‐specific esterases) which normally become active during crypt cell maturation. The activity of enzymes normally present mainly in the functional villus cells remained relatively unaffected by changes in crypt cell kinetics. A hypothesis of different regulation mechanisms of the proliferative activity in the intestinal crypt and a possible explanation of the different behaviour of various enzyme activities as a result of changes in crypt cell proliferation is discussed.
NUCLEAR INCORPORATION OF RADIOACTIVE DNA PRECURSORS AND PROGRESSION OF CELLS THROUGH S
Authors: Hirt A. , Wagner H. P.
Published: May 2008

Bone marrow blast cells of nine children with untreated acute leukaemia (five lymphoid, three myeloid, one monocytic), myeloid precursor cells of a haema‐tologically normal child and thoracic duct lymph cells of a patient with sclerodermia were pulse‐labelled in vitro with tritiated thymidine and/or tritiated cytidine. Combined radioautographic and cytophotometric techniques were used for the determination of the median nuclear size and the median grain count of labelled cells in different segments of S. It was found that the median grain count reached maximum values in the second or third quarter of S in all cell populations studied, and that the variation, during S, of the median grain count appeared to be independent of the median DNA synthesis times of the cell types investigated. In six cell populations a clear‐cut inverse relation existed between the number and the median grain count of labelled cells in different segments of S. In three populations this relation was less apparent and in two it was not found at all.
THE PREDOMINANT ROLE OF THE SPLEEN IN LYMPHOCYTE RECIRCULATION
Authors: Pabst R. , Trepel F.
Published: May 2008

Lymphocyte recirculation through the isolated pig spleen was studied by means of a perfusion system which kept the organ alive for a prolonged period of time. By changing the perfusate to a leucocyte‐enriched or cell‐free perfusate and taking serial arterial and venous samples, the numbers of lymphocytes which homed to or were released from the spleen were measured. In all experiments more lymphocytes homed than were released per minute. There was no apparent difference when autologous or allogeneic cells were used. The number of lymphocytes released depended on the number of lymphocytes homed previously.

During the phase of constant release up to 3‐3 × 106 lymphocytes were released per gram spleen per minute. From these values it can be extrapolated that up to 270 × 109 lymphocytes recirculate through the isolated pig spleen per day. Based on kinetic data from other species it is estimated that in the entire pig a total number of 300–400 × 109 lymphocytes recirculate per day. Thus, it can be concluded that the spleen is the most important organ for lymphocyte recirculation in the pig.
SERUM LEVELS OF COLONY STIMULATING FACTOR(S) AND THE GROWTH OF BONE MARROW CELLS IN DIFFUSION CHAMBERS
Authors: Beran Miloslav
Published: May 2008

Fluctuations in the body fluids of long‐ranged humoral substance(s) capable of stimulating the growth of bone marrow granulocytic and macrophage‐like cells in diffusion chamber cultures in vivo, was observed after whole body irradiation of mice. The fluctuation pattern was similar to that of the in vitro colony stimulating factor(s) of the sera of irradiated mice which indicates a relation between in vivo and in vitro active factor(s).
CELL KINETICS METHODS FOR CLINICAL USE: ASSESSMENT OF AUTORADIOGRAPHY AND 125I‐IODO‐DEOXYURIDINE WITH MOUSE EHRLICH TUMOUR
Authors: Jenkinson I. S. , Shuter B. J. , Wright P. N. M.
Published: May 2008

Superficial Ehrlich tumours in mice were used to assess how much information on cell kinetics could be obtained from only the simplest techniques of autoradiography, and in situ monitoring of 125I‐iodo‐deoxyuridine. These techniques were selected as being readily applicable to clinical situations. Intradermal tumours were studied from the earliest stages of rapid growth to large slow growing tumours with necrotic cores, as well as tumours undergoing regression. For comparison, intramuscular tumours were studied with systemic injections of radioactive DNA precursors. It was found that extensive information on cell production and loss rates was obtained from a single injection of tritiated thymidine followed by a single biopsy, or alternatively in vitro labelling of one minute biopsy specimen, and measurements of only the labelling index, together with a knowledge of the tumour's growth characteristics. Following a single localized injection of 125I‐iodo‐deoxyuridine, the loss rate of radioactivity measured in situ for a period of about 1 week provided an index of cell loss rate from the tumours.
MATRIX SIMULATION OF DUODENAL CRYPT CELL KINETICS
Authors: Roti Joseph L. Roti , Dethlefsen Lyle A.
Published: May 2008

The perturbed cellular kinetics of the duodenal crypt following a single injection of hydroxyurea (HU) have been simulated using matrix algebra. Following the direct effects of HU (S‐phase cytotoxicity and a G1/S block) the crypt cell kinetics undergo several alterations. Previously documented alterations include: (1) a temporary partial synchronization of the surviving cells, (2) a shortening of the cell‐cycle transit time, and (3) recruitment of normally non‐proliferating cells into active proliferation. These conclusions have been extended by constructing several different complex but theoretically possible recovery models and the validity of each of these models has been evaluated by simulating the following biological data: the number of cells in the S and M‐phase of the cell cycle, total viable cells per crypt, and the per cent labeled mitosis and the number of labeled cells following 3H‐TdR injections at 9 and 21 hr after HU treatment. The model which showed visually the best overall agreement with all sets of the data was chosen as ‘most probable’ and leads to the following interpretations. Immediately after the end of the HU block (i.e. 5 hr after HU injection) the modal cell‐cycle transit time is reduced to 8 hr. By 17 hr after HU, the modal transit time is increased to 10 hr. Repopulation of the proliferating compartment, i.e. restoration of the proliferating compartment back to the control value, occurs between 12 and 17 hr after HU injection and probably consists of both recycling of the proliferating cells (i.e. they do not progress up into the non‐proliferating compartment) and recruitment of the non‐proliferating cells into active proliferation. Also, the rate at which the non‐proliferating cells move onto the villi is reduced temporarily. The overall recovery process results in a crypt which temporarily is larger than control and produces villi cells at a rate which is faster than the control. The time when the crypt size and villus cell production rate return to normal cannot be established using the available data.
A NON‐DESTRUCTIVE METHOD FOR MEASURING INTESTINAL CELL TRANSIT TIME
Authors: Hagemann Ronald F. , Cooper John , Poulakos Lawrence
Published: May 2008

Villous exfoliation of intestinal epithelial cells, which had been previously labeled in the crypt with 125I‐iododeoxy‐uridine, can be detected by thyroidal accumulation of the liberated 125I‐. The latter can be monitored externally. The interval between labeled precursor injection and the steep portion of the thyroid activity accumulation curve corresponds to the intestinal cell transit time, as measured by destructive techniques, in three animal species. The technique allows estimations of intestinal cell transit time to be made on an individual basis, and can be expeditiously applied to large animals. Very small tracer doses are required for detection.
NUCLEOCYTOPLASMIC RATIO REQUIREMENTS FOR THE INITIATION OF DNA REPLICATION AND FISSION IN TETRAHYMENA
Authors: Worthington D. H. , Salamone M. , Nachtwey D. S.
Published: May 2008

Hydroxyurea (10 mM) arrests the exponential growth of Tetrahymena by blocking DNA replication during S‐phase. After removal of the hydroxyurea (HU), they have a long recovery period during which they are active in DNA synthesis. 3H‐TdR uptake showed that on completion of the recovery period, the cells divide (recovery division) and enter a cell cycle which lacks G1. The frequency, size and DNA content of the extranuclear chromatin bodies (ECB) formed at this division are all markedly increased (2–4) over the corresponding values obtained from exponential growth phase controls. Microspectrophotometric analysis of macronuclear DNA content (N) coupled with the cytoplasmic dry mass (C) values suggest that specific N to C ratios (N/C) are required for the initiation of DNA replication and fission: during a normal (exponential growth) cell cycle, both N and C double, but asynchronously, so that the N/C of both post‐fission‐daughter cells and pre‐fission cells is identical (standardized to N/C = 1) but late G1 cells have a low N/C. During a 10 hr exposure to HU, the N remains essentially the same whereas the C increases. When the HU is removed, the N increases by 4× and the C continues to increase until just prior to recovery division when it also reaches a value 4× that of the original daughter cells. Thus, the N/C = 1 is re‐established. The enlarged ECB formed during recovery division may function to lower the N/C in the daughter cells, which in turn may in some way stimulate immediate DNA replication, thus eliminating G1. The elimination of G1 (and shortening in a few subsequent cell cycles) allows less time for cytoplasmic growth and results in the return of the cells to the generation time and the N and C values observed prior to the HU treatment.
THE CELL PROLIFERATION KINETICS OF THE EMT6/M/AC MOUSE TUMOUR AT FOUR VOLUMES DURING UNPERTURBED GROWTH IN VIVO
Authors: Watson James V.
Published: May 2008

The cell proliferation kinetics of the EMT6/M/AC mouse tumour were determined at four different volumes between 1–5 mm3 and 175 mm3. The decrease in the growth rate between these volumes was mainly due to a decrease in the rate constant for cell production. A small increase in the rate constant for cell loss occurred, but this was thought to be insignificant. The cell loss factor increased from 40% at 1–5 mm3 to over 70% in the 175 mm3 tumours. An increase in the median cell cycle time, from 14‐1 hr to 18‐5 hr was also found between these same volumes. Results obtained for the NCTC fibrosarcoma and the R‐l rhabdomyosarcoma indicate that there may be a threshold volume in these sarcomas below which little or no cell loss takes place. This was not found in the EMT6/ M/AC tumour.