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Showing papers on "Cell growth published in 1968"


Journal ArticleDOI
TL;DR: Author commentary of the process is included to cover anticipation of the patient surge, transport of critical patients, and communication across all agencies--interhospital, local, state, and federal.
Abstract: The relation between cell proliferation and the vascular system in a transplanted mouse mammary tumour

715 citations


Journal ArticleDOI
TL;DR: Three clonal strains of epithelial cells established from a transplantable rat pituitary tumor have been serially propagated for 14–25 months and there has been no decrease in the rate of cell division nor decline in growth hormone secretion since the cells were established in culture.
Abstract: Three clonal strains of epithelial cells were established from a transplantable rat pituitary tumor. These strains have been serially propagated for 14–25 months. They were subcultured every 2–3 weeks. Cells of the original strain have increased by a factor of more than 1040. The generation times of the 3 lines were similar and ranged between 30 and 40 hr. Cells of all 3 strains synthesize growth hormone and secrete it into the culture medium. Growth hormone synthesized in vitro is indistinguishable from normal rat pituitary growth hormone as measured by micro-complement fixation and radioimmunoassay. The specific activity of growth hormone production was estimated to be 20–40 figμng cell nitrogen/24 hr for the most vigorous strain. There has been no decrease in the rate of cell division nor decline in growth hormone secretion since the cells were established in culture. (Endocrinology 82: 342, 1968)

660 citations


Journal ArticleDOI
TL;DR: The analysis of cell population kinetics indicates that the rate of entry of parenchymal cells into synthesis, after an initial burst of proliferative activity, was an orderly progression at 3–4%/hr; and most cells divided once and a few twice, a large proportion of the cell deficit being replaced by 72 hr after the onset of proliferation.
Abstract: The study concerns the kinetics of cellular proliferation in the different cell populations of the normal and regenerating rat liver. A detailed analysis is presented, which includes techniques of in vivo labeling of DNA with tritiated thymidine and high-resolution radioautography, of the temporal and spatial patterns of DNA synthesis and cell division in the parenchymal cells, littoral cells, bile duct epithelium, and other cellular components in the liver during the first 64 hr of regeneration after partial hepatectomy. The analysis of cell population kinetics indicates that (a) the rate of entry of parenchymal cells into synthesis, after an initial burst of proliferative activity, was an orderly progression at 3–4%/hr; (b) most cells divided once and a few twice, a large proportion of the cell deficit being replaced by 72 hr after the onset of proliferation; (c) Ts was ∼8.0 hr; Tgg2+m/2, 3.0 hr; and M, ∼1.0 hr. Littoral cell proliferation began about 24 hr after the onset of parenchymal cell proliferation; the rate of entry of littoral cells into synthesis was greater than 4%/hr. Interlobular bile duct cell proliferation lagged well behind the parenchymal and littoral cell populations both in time and extent of proliferation.

285 citations


Journal ArticleDOI
27 Dec 1968-Science
TL;DR: Dibutyryl-adenosine 3',5'-monophosphate, reported to have a greater activity than adenosine 1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,34
Abstract: Adenosine 3',5'-monophosphate, at a concentration of 40 micrograms per milliliter, inhibits the growth of HeLa and strain L cells in culture. The inhibition becomes progressively greater during the incubation of the cells. Adenosine 5'-monophosphate and adenosine, metabolites of adenosine 3',5'-monophosphate, do not affect the growth of either cell culture. This suggests that 3',5'-monophosphate enters the cell without alteration. Dibutyryl-adenosine 3',5'-monophosphate, reported to have a greater activity than adenosine 3'5'-monophosphate on several tissues, inhibited the growth of the cells much less.

237 citations


Journal ArticleDOI
01 Sep 1968-Nature
TL;DR: In this article, the authors present indirect evidence that increased levels of cyclic-AMP may decrease cell growth in culture and describes an attempt to test the hypothesis that the regulation of cyclIC-AMP levels differs in normal and virus transformed cells.
Abstract: THERE is now substantial evidence that the intracellular concentration of adenosine 3′5′ cyclic monophosphate (cyclic-AMP) is an important factor in the hormone regulation of some specialized functions of the cells of a number of tissues1,2. The intracellular level of cyclic-AMP is chiefly determined by the balance between its formation from 5′ATP by adenyl cyclase and its degradation to 5′AMP by a specific 3′5′ cyclic phosphodiesterase. If this balance were altered by mutation, teratogenic differentiation, or infection, there could be profound changes in the functions of the cell. An alteration leading to a lower level of cyclic-AMP might lead to the increased aerobic glycolysis and decreased specialized function commonly observed after neoplastic transformation (chemical, “spontaneous” or viral). This paper presents indirect evidence that increased levels of cyclic-AMP may decrease cell growth in culture and describes an attempt to test the hypothesis that the regulation of cyclic-AMP levels differs in “normal” and virus transformed cells.

215 citations


Journal ArticleDOI
TL;DR: It appears that high levels of prostatic DNA polymerase are demonstrable only around the times that prostatic cells are actively engaged in DNA synthesis, which is related to the relative contribution of cell proliferation to the overall growth of androgen-sensitive tissues.

196 citations


Journal ArticleDOI
J. Jarmolych1, A.S. Daoud1, J. Landau1, K.E. Fritz1, E. McElvene1 
TL;DR: Segments of pig aortic medial tissue, cultured in a semisynthetic medium, develop a new growth starting about the fourth day, where most cells in this new growth are primitive cells and fibroblast-like cells with only a few modified smooth muscle cells.

111 citations


Journal Article
TL;DR: With each complete turn of the cell through its life cycle, all of the structural elements and functional capacities of the nucleus and cytoplasm undergo a doubling, and the regulation of the growth and production of a subcellular part must be tied into itsfuncional contribution to the cell.
Abstract: With each complete turn of the cell through its life cycle, all of the structural elements and functional capacities of the nucleus and cytoplasm undergo a doubling. All of these events, such as mitochondrion and ribosome production, formation of new membranes, doubling in the capacities for glycolysis and lipid metabolism, chromosome reproduction, etc., must be pre cisely interrelated and coordinated through a variety of reg ulatory mechanisms that assure balanced cell growth and cell function. These integration mechanisms are the central element of growth, and the lack of specific information about their physiologic or molecular bases puts a serious limit on our understanding of cell reproduction. New mitochondria, for example, are produced by fission of the old (28, 29), but how mitochondrial growth and fission are continuously adjusted to the pace of all the other component parts of cell growth is unknown. In a general sense the regulation of the growth and production of a subcellular part must be tied into its func tional contribution to the cell; for example, mitochondrial in crease must somehow be linked to function through some such condition as the concentration of ATP, ADP, diphosphopyridine nucleotide (reduced) or triphosphopyridine nucleotide (reduced) etc. Such specific information on the relation be tween function and growth is still not available for any cellular organelle or part. Relatively little attention is given at present to problems of cytoplasmic growth and reproduction because the pace of cell progress through the life cycle appears to be governed principally by the nuclear events of chromosome replication and segregation; all other growth activities are ultimately geared directly or remotely to the accomplishment of the chromosomal processes. The explanations of how the cell cycle is driven forward, of the regulation of cell cycle progress, or of how reproduction of cells is controlled within an organism all hinge primarily on successful analysis of the regulation of chromosome replication and segregation. The subdivision of the cell life cycle into G1( S, G2, and D (or M) reflects this attitude, since these subsections are defined by what the chromosomes are doing or aren't doing rather than

108 citations


Journal ArticleDOI
TL;DR: Various lines of evidence lead to the conclusion that the cellular differentiation in the shoot apex is organized and a relatively stable process.
Abstract: A B S T R A C T Somatic mutations were induced in maize embryos in order to follow the albino-tissue patterns in mature plants. A reconstruction of cellular development in the shoot apex has been attempted. Two strains of maize were employed, wd/Yg9 and pastel-8549/y, for seed irradiation with gamma rays. After mature plants had developed from this radiated seed, the sectored plants were analyzed in detail for their patterns of albino tissue. The location and frequency of these patterns were correlated with cell number at various sites of the initial shoot apex in order to deduce the number of cells contributing to each frequency class. Various lines of evidence lead to the conclusion that the cellular differentiation in the shoot apex is organized and a relatively stable process. Apparently a few cells in the apical dome provided daughter tissue for the upper half of the maize plant. Various sector patterns are diagrammed and the position of their albino tissue is explained in relation to the location of a specific cell in the apex.

79 citations


Journal ArticleDOI
TL;DR: It is suggested that linear growth represents constant uptake of all major nutrient factors during the cycle, and that constant uptake in turn is established by the presence of a constant number of functional binding or accumulation sites for each growth factor during linear growth of the cell.

70 citations


Journal ArticleDOI
TL;DR: Initial recovery of the ability to divide has an obligate requirement for protein synthesis but no corresponding requirement for nucleic acid synthesis during the period when original messenger remains intact.


Journal ArticleDOI
TL;DR: Rhodotorula gracilis growing in batch culture exhibited acceleration, exponential and linear phases of growth and it is suggested that the rate of lipid production was not stimulated but remained constant, the apparent increase being almost entirely due to the absence of cell proliferation.
Abstract: SUMMARY Rhodotorula gracilis growing in batch culture exhibited acceleration, exponential and linear phases of growth. In a fourth phase, following nitrogen exhaustion, the concentration of lipid in the culture increased, but it is suggested that the rate of lipid production was not stimulated but remained constant, the apparent increase being almost entirely due to the absence of cell proliferation. No significant changes occurred in the fatty acid composition of the lipid when nitrogen was exhausted. At low pH values, growth of the organism was retarded, but the lipid production rate increased although the final concentration of lipid remained the same. The ratio of unsaturated to saturated fatty acids also decreased principally due to a lowered concentration of oleic acid but the concentration of myristic, stearic, linoleic and linolenic acids increased.

Journal ArticleDOI
20 Jul 1968-Nature
TL;DR: Evidence is presented that the growth of cells is also inhibited at higher temperatures as a result of the presence of the temperature sensitive R factor.
Abstract: IT was shown earlier1 that an R factor determining resistance to kanamycin is spontaneously eliminated at 42° C, and its conjugal transfer is inhibited at this temperature. This temperature sensitivity was ascribed to temperature sensitive replication of the R factor. We present here evidence that the growth of cells is also inhibited at higher temperatures as a result of the presence of the temperature sensitive R factor.

Journal ArticleDOI
TL;DR: It is concluded that liver macrophages derived from either of two different precursors in populations of recirculating lymphocytes and bone marrow cells respectively can proliferate preferentially, according to the nature of the reticulo-endothelial stimulus.
Abstract: The origin of dividing liver macrophages during states of intense reticulo-endothelial stimulation has been studied in mice by means of the T 6 marker chromosome. The cells were isolated for cytological analysis by means of Garvey’s technique of collagenase and trypsin digestion. During the proliferative phase of graft-versus-host ( GVH ) reaction in the strain combination C 57BL → (C57BL x CBA-T6T6)F 1 , practically all liver macrophages in mitosis were of donor karyotype, even when relatively pure suspensions of thoracic duct small lymphocytes were used as the donor cells. Several lines of evidence established that the dividing cells analysed were part of a macrophage response. The isolated cells in mitosis had macrophage characteristics which reflected the cell proliferation examined in histological sections. This proliferation was largely restricted to the liver sinusoids and to cells with phagocytic properties. The same proportion of these cells appeared to be actively phagoctyic before their arrest in metaphase by Colcemid during GVH reaction as was found in normal mice. Furthermore, more than 70% of the liver sinusoidal cells which incorporated 3 H -thymidine were demonstrably phagocytic before and/or after labelling. Liver macrophage proliferation was greatly depressed by splenectomy 24 h after injection of donor cells, although cells of donor karyotype were still predominant. Similar techniques have been applied to syngeneic radiation chimaeras—( CBA x CBA-T6T6 ) F 1 mice ‘repopulated’ with CBA- T6T6 lymphocytes and CBA bone marrow. When Corynebacterium parvum vaccine was applied as a stimulant, two-thirds of dividing liver macrophages were found to be of lymphocyte origin and one-third or less derived from a precursor in bone marrow cells. Using partial hepatectomy to stimulate macrophage proliferation in these chimaeras, however, it was found that the overwhelming majority were derived from the bone-marrow precursor. The phagocytic property of the majority of proliferating cells was established by combined colloid and 3 H-thymidine labelling. It is concluded that liver macrophages derived from either of two different precursors in populations of recirculating lymphocytes and bone marrow cells respectively can proliferate preferentially, according to the nature of the reticulo-endothelial stimulus. Evidence from a variety of sources supports the contention that the bone-marrow precursor cell represents the major source of ‘normal’ macrophages. Whether the precursor amongst thoracic duct cells is identifiable with any previously recognized category of lymphocyte is not yet known. Its utilization has only been detected so far during conditions of intense reticulo-endothelial stimulation.

Journal ArticleDOI
01 Mar 1968
TL;DR: Proboscis primordia (labial discs) from four Drosophila species were cultivated in the abdomens of adult females and then transplanted into larvae.
Abstract: Proboscis primordia (labial discs) from fourDrosophila species were cultivated in the abdomens of adult females and then transplanted into larvae. After metamorphosis, the imaginal structures of the implants were studied both in homoplastic and heteroplastic transplantations. - After at least two days of culturing in an adult host of the same species one labial disc furnishes the same structures as one pair of discsin situ. - For the formation of such a symmetrical duplicate structure proliferation is required. When the blastema has reached a certain size, it becomes arranged into two adjacent areas i.e. - two connected proboscis halves of approximately normal size (homonomous arealisation). - By cell multiplication, the state of determination of the single cell is passed onto the daughter cells (cell heredity). These organize themselves along an axis of symmetry. - After the transitory culturing labial discs transdeterminate to such allotypic structures as palpus, leg or antenna. - Transdetermination occurs only in proliferating cells and, in symmetrical preparations, only in the newly developed half. - The frequency and the pattern of allotypic structures varies greatly in the four species under investigation. The differences are specific for the species and are not due to different proliferation activity. - There is a positive correlation between the growth of the blastema, the duration of culture, and the frequency of transdetermination. This finding indicates that cell reproduction is relevant to transdetermination. - Heteroplastic transplants of labial discs betweenD. melanogaster andD. simulans develop autonomously with regard to proliferation and transdetermination in both combinations. - Proboscis primordia fromD. hydei change their properties of transdetermination inD. melanogaster andD. virilis. In the first case, development of leg and antenna is inhibited. In the second case, the frequency of transdetermination diminishes. These differences are not due to reduced proliferation in a different species of host. They are based on some other effect of the culture medium.

Journal ArticleDOI
TL;DR: The results indicated that the number of G1 cells induced to enter S increased directly with the spurt duration and that cells could be positioned and retained in the S and/or G2 periods by varying the duration of thespurt.
Abstract: A stationary phase in the root meristem of excised pea roots was established by prolonged carbohydrate deprivation in sterile culture medium. When the stationary phase had been established, cells that had collected in the G1 period of the mitotic cycle were induced to enter the S stage by subjection to relatively short intervals of carbohydrate provision (sucrose spurts). Progression and cycle location of the G1 cells induced to enter S were measured with tritiated thymidine and radioautography. The results indicated that the number of G1 cells induced to enter S increased directly with the spurt duration and that cells could be positioned and retained in the S and/or G2 periods by varying the duration of the spurt. The data support the hypothesis that S and maybe M stages have a relatively larger dependence on carbohydrate availability, and presumably a greater energy requirement, than G1 and G2.


Journal ArticleDOI
TL;DR: Cell cycle times were drastically shortened by transplantation and transplantation 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%.
Abstract: 1 Ehrlich ascites tumor cells collected from donor mice on the 5th day after inoculation were injected into the peritoneal cavity of new recipient mice. 2 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. 3 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%.


01 Jan 1968
TL;DR: The filamentous species, Penicillium lilacinum and Trichophyton schoenleinii, and the dimorphic species, Histoplasma capsulatum, developed budding yeastlike cells when grown in a liquid medium with a low oxidation-reduction potential.
Abstract: A device for the adjustment, maintenance, and monitoring of a desired oxidation-reduction potential in a liquid environment is described. The filamentous species, Penicillium lilacinum and Trichophyton schoenleinii, and the dimorphic species, Histoplasma capsulatum, developed budding yeastlike cells when grown in a liquid medium with a low oxidation-reduction potential. When the organisms were inoculated into fresh medium, they returned to the filamentous condition as the oxidation-reduction potential was restored to a more positive (oxidizing) environment.

Journal ArticleDOI
TL;DR: Cell life and the duration of the deoxyribonucleic acid synthesis phase (S) were ascertained in five stratified squamous epithelia in mice by simultaneous injection of colchicine and tritiated thymidine with sacrifice 6 h later.

Journal Article
TL;DR: The time course of immunoglobulin accumulation and cell proliferation indicated that the cells were able to synthesize and secrete immunoglolobulins actively only while they are able to proliferate.
Abstract: The production of immunoglobulins by three established human hematopoietic cell lines has been studied. RPMI no. 8235 produced only κ type IgG, RPMI no. 4666 produced κ type IgA and free κ type light chains indicating an imbalance of heavy and light chain synthesis. These two cell lines are both derived from the buffy coat of patients with chronic myelogeneous leukemia. The third cell line RPMI no. 8226, which is derived from the buffy coat of a patient with multiple myeloma, produced only free λ type light chains very actively without any indication of the production of heavy chains, and appears to be a culture of cells belonging to a malignant plasma cell line. The immunoglobulins produced by these cell lines resemble pathologic immunoglobulins produced in individuals with multiple myeloma. Each immunoglobulin was of a single light chain type and showed a well defined electrophoretic mobility. The time course of immunoglobulin accumulation and cell proliferation indicated that the cells were able to synthesize and secrete immunoglobulins actively only while they were able to proliferate. In their most active phases, the cells of both RPMI nos. 8235 and 4666 synthesized and secreted about 3 µg of immunoglobulins per 105 cells per day, whereas the cells of RPMI no. 8226 produced about 20 µg of light chains per 105 cells per day.

Journal ArticleDOI
Per Eker1
TL;DR: Data are presented which indicate that deoxycytidylate deaminase as well as thymidylates kinase is subject to feedback inhibition by deoxythymidine nucleotides, and inhibition of growth by hydroxyurea was likewise associated with a strong increase in deoxymidine kinase activity, an effect which was inversely related to the growth rate of the cell cultures.

Journal ArticleDOI
23 Aug 1968-Science
TL;DR: Dispersion of confluent monolayers of BHK21 cells with ethylenediaminetetraacetate yields a material that inhibits cell proliferation, whereas identical extraction of polyoma-virus-transformed cells provides material which enhances cellular proliferation.
Abstract: Dispersion of confluent monolayers of BHK21 cells with ethylenediaminetetraacetate yields a material that inhibits cell proliferation, whereas identical extraction of polyoma-virus-transformed cells provides material which enhances cellular proliferation. The material was partially characterized.

Journal ArticleDOI
TL;DR: Experiments with double labelling with 3HTdR and 32PO4 indicated that crowding in fact affected DNA synthesis in human, hamster and mouse cells.

Journal Article
TL;DR: The results suggest that naturally occurring sugar constituents of cells may play a unique role in influencing cell growth and metabolism.
Abstract: Summary Studies concerning the effects of naturally occurring simple sugars on the morphology and metabolism of various mammalian cell lines further illustrate the selective effects of different individual sugars on specific cell lines. Attempts to characterize the selective effects of l-fucose on 3T3 fibroblasts showed that the marked changes in morphology and inhibition of incorporation of radioactive precursors were reversible. Also, the plating efficiency of 3T3 cells grown in medium containing l-fucose for 24 hours was not diminished. Studies of the sequence of inhibition of incorporation of radioactive precursors in fucose-containing cultures showed that uridine incorporation was decreased before leucine and thymidine. In contrast to the striking effects of l-fucose on rapidly growing cultures of 3T3 cells, the addition of this sugar to confluent cultures caused no apparent effects. The mechanisms by which l-fucose causes these changes in 3T3 cells are unknown. However, it does not appear to be caused directly by interference with the uptake or utilization of glucose. Furthermore, the selective inhibition by l-fucose appears to require very little of this sugar to be taken up by the cells. Parallelisms between the characteristics of inhibition by l-fucose and those of cell contact inhibition of mitosis raise the possibility that similar mechanisms operate in both phenomena. Regardless of the mechanisms responsible for the selective effects of l-fucose, the results suggest that naturally occurring sugar constituents of cells may play a unique role in influencing cell growth and metabolism.

Journal ArticleDOI
TL;DR: The results supported the view that the nucleus controls cell movement by mechanisms other than those of controlling cell reproduction.

Journal ArticleDOI
TL;DR: The limited usefulness of intracerebral injection of tritiated thymidine is discussed and this and histological changes in the layer could be attributed to the effects of endogenous irradiation of nuclei from newly formed radioactive DNA.

Book ChapterDOI
TL;DR: The potential usefulness of morphological-functional criteria in studying intermitosis is focused on, and particularly on the period of cell preparation for mitosis, which is the outgrowth of attempts to correlate morphological developmental forms with developmental changes in function.
Abstract: Publisher Summary This chapter focuses on the potential usefulness of morphological-functional criteria in studying intermitosis, and particularly on the period of cell preparation for mitosis. It discusses the developmental phases in intermitosis and the preparation for mitosis of mammalian cells in vitro . Mammalian cells possess the property of changing their developing morphological forms, which can be correlated with changes of cell function during growth. This property makes them even more suitable objects for the analysis of cell growth and development than bacteria. The division of intermitosis happens into six morphological-functional developmental phases, mitosis being the seventh phase. This division resulted from study of the kinetics of growth, development, and division of L-strain cells in vitro, cytochemical analysis, and determination of the rate of DNA, RNA, and protein synthesis of these cells. It is the outgrowth of attempts to correlate morphological developmental forms with developmental changes in function. The direct consequence of this is the possibility of correlating functional states and changes of the cell with determined developmental forms, instead of such a variable feature as generation time or the duration of each developmental phase of the cell in intermitosis. The chapter also discusses the functional changes in intermitosis, morphological changes during intermitosis, and some results of analyses of intermitosis applying the concept of developmental phases.