Showing papers on "Cell growth published in 1972"

Difference in the Cyclic Adenosine 3′,5′-Monophosphate Levels in Normal and Transformed Cells

Abstract: CYCLIC 3′5′-adenosine monophosphate (cyclic AMP) regulates many physiological phenomena1,2. Cellular morphology changes when the dibutyryl derivative of cyclic AMP is added in vitro to the nutrient media of cultured mammalian cells3–6. Dibutyryl cyclic AMP has also been shown to restore controlled growth to transformed cells3, change the cell's surface architecture3,7 and induce axon formation8 with an accompanied increase in acetylcholinesterase activity9 in neuroblastoma cells growing in culture. These effects suggest that the cyclic AMP moiety may have some basic regulatory action on cell growth and cell specialization.

A Unifying Hypothesis Concerning the Nature of Malignant Growth

Abstract: It is suggested that the crucial change in a malignant cell is an alteration in the cell surface membrane that results in increased internal concentrations of nutrients that regulate cell growth.

The synthesis of acidic chromosomal proteins during the cell cycle of HeLa S-3 cells. I. The accelerated accumulation of acidic residual nuclear protein before the initiation of DNA replication.

Abstract: The synthesis and accumulation of acidic proteins in the tightly bound residual nuclear fraction goes on throughout the cell cycle of continuously dividing populations of HeLa S-3 cells; however, during late G1 there is an increased rate of synthesis and accumulation of these proteins which precedes the onset of DNA synthesis. Unlike that of the histones, whose synthesis is tightly coupled to DNA replication, the synthesis of acidic residual nuclear proteins is insensitive to inhibitors of DNA synthesis. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of acidic residual nuclear proteins shows different profiles during the G1, S, and G2 phases of the cell cycle. These results suggest that, in contrast to histones whose synthesis appears to be highly regulated, the acidic residual proteins may have a regulatory function in the control of cell proliferation in continuously dividing mammalian cells.

Effects of corticosteroids on the biochemical maturation of rat brain: postnatal cell formation.

Abstract: (1) Treatment with cortisol acetate (0.2 mg daily during the first 4 days after birth) reduced the rate of growth in the rat: at 35 days of age the body weight was reduced by 50 per cent and the brain weight, depending on the region, by up to 30 per cent. (2) In the brain the normal increase in cell number was severely inhibited during the period of cortisol treatment; this resulted in a final deficit in cell number of about 20 per cent in the cerebrum and 30 per cent in the cerebellum. (3) To determine whether cortisol affected primarily cell formation or cell destruction the labelling of brain DNA was studied 1 h after a subcutaneous injection of 20 Ci/100 g [2-14C]thymidine. In the controls the amount of labelled DNA increased by a factor of two in the cerebrum and seven in the cerebellum during the period 2-13 days, and it decreased to 40 and 27 per cent of the peak values in the cerebrum and cerebellum respectively in the following 7 days. The results indicated that mitotic activity is higher in the cerebellum than in the cerebrum in the 2nd week of life. It would appear that in the cerebrum appreciable cell death accompanies new cell formation, especially during the period 13-35 days of age. (4) Cortisol treatment affected cell division rather than cell destruction in the brain since it strongly inhibited the incorporation of [2-14C]thymidine into DNA. The inhibition was severe during the period of treatment but it did not result in a lasting fall in mitotic activity. At the age of 13 days the amount of labelled DNA formed approached the normal level and it was twice that in controls at 20 days, indicating a tendency for compensating cell deficit by an accelerated mitotic activity. Nevertheless, massive cell proliferation ceased at about the same age as in normals; the labelling of DNA decreased markedly between 13 and 20 days after birth, and the DNA content did not increase after the age of 20 days. (5) In contrast to the marked effect on cell number, cortisol treatment did not influence significantly the maturational changes related to average cell size (DNA concentration) or the chemical composition of cells (RNA/DNA and protein/DNA).

Replication of the Parvovirus MVM I. Dependence of Virus Multiplication and Plaque Formation on Cell Growth

Abstract: A plaque assay has been developed for the minute virus of mice. The infectious unit is a single particle. Plaque size is determined by the extent of cell division in the infected monolayer. Infection of quiescent and serum-stimulated cells suggests that virus multiplication depends on host function(s) that are not normally expressed in resting cells.

Effect of adenosine 3'-5'-cyclic monophosphate on cell proliferation

Abstract: Secondary cultures of human diploid fibroblasts, which demonstrate density-dependent inhibition of cell growth, were used to study the effect of adenosine 3'-5'-cyclic monophosphate (cAMP) on cell proliferation. DNA synthesis in nonconfluent cultures and in contact-inhibited cultures stimulated to grow by refeeding with fresh medium was found to be inhibited by exogenous cAMP. The properties of this inhibition of DNA synthesis, together with the alterations in cAMP metabolism observed in confluent cultures of cells stimulated with fresh medium to resume growth, strongly suggest that cAMP is involved in contact-inhibition of cell proliferation.

Neuraminidase stimulates division and sugar uptake in density-inhibited cell cultures.

Abstract: THE proliferation of normal cells stops when the cultures have formed confluent monolayers; this process is termed density-dependent inhibition of growth (DDI). The cells can be released from DDI by proteolytic enzymes and other substances acting on the cell surface1, indicating that the cell surface may be important in regulating cell proliferation. Sialic acid residues also may be important in this regulation. Growing and virus-transformed cells contain less sialic acid in glycolipids2 and possibly also in glycoproteins3 than normal resting cells. We report direct evidence that the control of cell growth is related to sialic acid residues on the cell surface. Small concentrations of neuraminidase initiate proliferation in stationary cell cultures and cause an early increase in sugar uptake.

Levels of cyclic AMP in sparse and dense cultures of growing and quiescent 3T3 cells.

Abstract: 3′ 5′-CYCLIC adenosine monophosphate (cAMP) has been reported to be involved in the regulation of cellular growth1–5. cAMP levels are low in growing 3T3 cells whereas they are increased in resting cells in confluent cultures5. SV40 or polyoma virus transformed 3T3 cells as well as 3T6 and BHK cells, which reach high cell densities and do not become quiescent, are characterized by a low serum requirement and low levels of cAMP6 (W. Seifert, unpublished results). Therefore, it has been suggested that the growth pattern of normal cells (for example, density dependent cessation of growth) is controlled by intracellular cAMP levels2,5,6: high cellular levels of cAMP are considered to be growth inhibitory while depressed cellular cAMP levels may lead to a continuation of growth1,2,5. It has been suggested1,8 that the levels of cAMP in resting cells are increased as a consequence of contact between cells which may lead to a stimulation of the membrane bound adenyl cyclase. A negative signal which would lead to the inhibition of DNA synthesis as a consequence of cell-cell contact has been suggested7. Evidence from studies on inhibition of cell growth by (But)2cAMP and/or theophylline points to cAMP as a possible mediator1,2,8. Serum, however, antagonizes the growth inhibiting effect of (But)2cAMP9,10.

Dissociation of MIF Production and Cell Proliferation

Abstract: The principal methods currently employed to explore the mechanism of cell-mediated immunity are blast cell transformation, production of soluble mediators and direct lymphocyte-target cell cytotoxicity. It is important to understand the nature of the cell detected in each of these assays in vitro , and to establish its relationship to the cell-mediated response in vivo . While it appears clear that the induction phase in sensitization requires the proliferation of stem cells to fully competent lymphocytes, there is considerable evidence in vivo to suggest that the effector arm of the response does not require cell proliferation. The most obvious example in vivo of this is the well known radiation resistance of the cell-mediated immune response in comparison to the humoral responses (1, 2). Additionally, cells treated with mitomycin C, under conditions in which they can synthesize some RNA and protein but cannot divide, are capable of effecting passive transfer (3).

Role for Protein Phosphorylation in Meiosis and in the Early Cleavage Phase of Amphibian Embryonic Development

Abstract: DURING maternal embryogenesis, the vertebrate egg is blocked in meiotic prophase. At ovulation it proceeds to the metaphase of the second meiotic division, which is complete after fertilization or an artificial stimulus. The first mitotic division occurs about three hours later, and is followed by a series of rapid mitoses without cell growth. In amphibia, the cell cycle is completed in less than an hour at 180° C. During early cleavage in Xenopus there is reportedly1 no G1 phase, and the G2 is either absent or very short.

Requirement for adherent cells in the primary and secondary immune response in vitro

Abstract: Treatment of spleen cells with iron powder, followed by removal of the iron with a magnet, was found to be a simple and reliable method for obtaining a population of non-adherent cells, which does not give an antibody response against heterologous red cells in vitro. It was possible to reconstitute the antibody response to 40 - 90% of that obtained with untreated cells by addition of irradiated or non-irradiated adherent spleen cells. The secondary response was also depressed by treatment with iron and it could be completely reconstituted with adherent cells from normal mice. Removal of adherent cells also caused a depression of spontaneous cell proliferation, which could be reconstituted by addition of adherent cells. Comparative kinetic studies on cell proliferation and antibody response indicated that the adherent cells are necessary for a normal cell proliferation and that they do not act by breaking down the antigen. This conclusion was further supported by the finding that an immune response against a soluble sheep red cell antigen was also dependent on adherent cells.

Effects of Protease Inhibitors on Growth of Hamster Tumor Cells in Culture

Abstract: Beef pancreas trypsin inhibitor has been shown to promote parallel alignment of hamster tumor cells in culture and to increase the adhesiveness of rounded cells. It has a slightly depressing effect upon cell proliferation. Soybean inhibitor depressed cell proliferation but had no effect upon cell alignment. Egg white inhibitor had no effect upon proliferation or cell alignment. The synthetic protease inhibitor N -α- p -tosyl-l-lysine chloromethyl ketone HCl had no effect upon cell alignment but depressed cell proliferation. It was toxic in concentrations in excess of 20 µm. Beef pancreas trypsin inhibitor had no effect upon cell proliferation or cell interaction of nontumorigenic hamster embryo cells in culture. The results suggest that some aspects of the morphology and social behavior of the tumor cells studied may be associated with protease activity that can be inhibited by beef pancreas trypsin inhibitor.

Proliferative parameters of mammalian cell systms and their rôle in tumor growth and carcinogenesis.

Abstract: The molecular processes associated with DNA replication and cell division, the mechanisms responsible for the regulation of cell proliferation, and the kinetic analysis of cell proliferation in simple and complex systems are topical problems of current research in cell biology. Their fundamental importance for many aspects of cancer research need not be stressed. In the following, some of the proliferative properties of normal and malignant mammalian cell systems will be briefly discussed in relation to problems of tumour growth (including a few questions of cancer therapy) and carcinogenesis. General Aspects

Effect of allogeneic cell interaction on the primary immune response in vitro. Cell types involved in suppression and stimulation of antibody synthesis.

Abstract: A graft-versus-host (GVH) reaction was induced in F1 hybrid mice by the inoculation of spleen cells from one of the parental strains. One week later the spleen cells from the recipients were cultured during the conditions for obtaining a primary immune response in vitro described by Mishell & Dutton (1967). It was found that the antibody response against the thymus-dependent antigen sheep red cells (SRC), as well as the thymus-independent antigen lipopolysaccharide from Escherichia coli 055:B5 (CPS) was markedly depressed. Spleen cells from mice subjected to a GVH reaction (GVH cells) also inhibited the antibody response of normal cells in vitro. The inhibitory effect of the GVH cells on normal cells was not sensitive to treatment with anti-θ serum, but could be completely abolished by treatment with iron powder, which removes adherent cells. By culturing cells of two different mouse strains together in vitro it was possible to obtain stimulation or inhibition of the antibody response depending on the total cell number per dish. The relation of these results to the phenomenon of antigenic competition is discussed. It is suggested that antigenic competition is caused by a non-specific inhibition of cell proliferation, possibly mediated by a locally acting factor. Both thymus-derived and bone marrow-derived cell lymphocytes are affected by the phenomenon. The cells initially responsible for the inhibition seem to be antigen-activated thymus-derived cells (T-cells), which by secondarily activated cells such as macrophages inhibit other cells. A GVH reaction, which generally leads to antigenic competition may, when less pronounced, cause stimulation of the antibody response.

Role of Transcription in the Temporal Control of Development in Caulobacter crescentus

Abstract: The requirement for transcription during development of the stalked bacterium, Caulobacter crescentus, was studied with synchronous cultures of swarmer cells. The developmental pattern in these bacteria was first established by determination of the times at which specific changes in cell structure and function occurred. These changes could be divided into those characteristic of (a) development of the swarmer cell into the stalked cell: loss of motility and synthesis of the stalk, and (b) development of the stalked cell into the asymmetric dividing cell: chromosome replication, synthesis of the flagellum, motility, and division. The effect of rifampin in blocking several of these steps—loss of motility, initiation of chromosome replication, and cell division—indicates that RNA synthesis is required throughout the cell cycle for normal differentiation.

Cell division in the marine slime mold, Labyrinthula sp., and the role of the bothrosome in extracellular membrane production

Abstract: Electron microscopic observations of vegetative cell division inLabyrinthula indicate that the specialized invaginations of the cell surface called bothrosomes arisede novo between newly divided daughter cells and function in the production of the membrane-bound extracellular matrix or slimeways. Protocentrioles are formed before each division and persist through cell separation but are not found in interphase cells. Cytokinesis begins after the completion of mitosis and occurs by vesicle accumulation and fusion, an unusual cytokinetic mechanism reminiscent of zoospore cleavage. Cell elongation after cytokinesis is accompanied by elongation of the Golgi apparatus and the appearance of non-spindle microtubules.

Dependence of Cell Division on the Completion of Chromosome Replication in Caulobacter crescentus

Abstract: The relationship between chromosome replication and cell division in the stalked bacterium Caulobacter crescentus has been investigated. Two compounds, hydroxyurea and mitomycin C, were found to inhibit completely deoxyribonucleic acid (DNA) synthesis while allowing continued cell growth and elongation. When these inhibitors were added to exponentially growing cultures, cell division stopped after 38 min when hydroxyurea was used and after 33 min when mitomycin C was used. The period of continued cell division corresponds closely to the period previously determined for the postsynthetic gap (G2) in the DNA cycle of this organism. These results indicate that cell division is coupled to the completion of chromosome replication in C. crescentus.

Relationship between organization of mammary tumors and the ability of tumor cells to replicate mammary tumor virus and to recognize growth-inhibitory contact signals in vitro.

Abstract: Mammary tumor virus (MTV) replication was confined primarily to cells organized as acini in intact mouse mammary glands. Primary mammary tumors maintained a high degree of acinar organization and cells therein continued to replicate MTV vegetatively. Nonacinar mammary cells, derived by serial transplantation of acinar tumor cells, no longer actively replicated MTV. This suggests that phenotypic differences exist among mammary epithelial cells in their ability to support virus replication, that a fundamental relationship exists between the organization of epithelium for secretion and active virus replication, and that this relationship is not altered as a primary consequence of neoplastic transformation. Mammary epithelial cells from pregnant, non-tumor-bearing, MTV-infected BALB/cfC3H mice or from acinar mammary tumors from a number of mouse strains were grown in primary monolayer cultures. Such cell cultures under the influence of insulin and cortisol exhibited the ability to organize into discrete three-dimensional structures called “domes.” MTV replication in such cultures took place primarily in cells within the organized domes. Cells cultured from nonacinar tumors did not exhibit any propensity to organize into domes, nor did they replicate MTV in primary culture. This suggests that the cell organizational requirement for MTV replication observed in vivo is conserved in primary culture. Dome formation is not an effect of virus replication, as cells from uninfected BALB/c animals organized into domes in culture without concomitant MTV replication. Growth-regulating signals, exerted between contiguous cells in cultures of non-MTV-infected mammary epithelium, were not modified by the occurrence of active virus replication nor as a direct consequence of neoplastic transformation. Cells derived from nontumor BALB/cfC3H glands and from spontaneous tumors exhibited cell growth kinetics, saturation densities, and deoxyribonucleic acid synthesis kinetics nearly identical to those of noninfected normal mammary epithelium in primary culture. Cell to cell growth regulatory signals were modified in cultures of nonalveolar tumor cells wherein evidence of overgrowth is documented.