Showing papers on "Cell growth published in 1969"
TL;DR: La duree des differentes phases du cycle cellulaire est mesuree par la methode des mitoses marquees, apres injection in vivo of thymidine marquee au tritium, pendant la croissance des tumeurs, and apres irradiation.
259 citations
TL;DR: After irradiation in the plateau phase of growth, not only do these human cells recover from sub-lethal radiation damage, but potentially lethal damage is repaired if the cells are allowed to remain in the stationary phase for some time after irradiation.
Abstract: WHEN monolayer cultures of mammalian cells are allowed to reach the stationary or plateau phase of growth, overall DNA synthesis decreases markedly. This is chiefly a result of the appearance of many non-proliferating cells which remain in the presynthetic (G1) stage of the cell cycle, while the cell concentration remains approximately constant because the lowered rate of cell division is balanced by the sloughing of dead cells into the nutrient medium1,2. Such cultures are interesting to radiobiologists because they represent an in vitro cell renewal system which has several of the characteristics of human malignant tumours. When Chinese hamster cells were irradiated in the plateau phase of growth, the slope of the survival curve was similar to that obtained with exponentially growing cultures, but the cells did not accumulate and repair sub-lethal damage3. I have investigated the effects of radiation on stationary cultures of a line of cells derived from normal human liver (Chang)4. After irradiation in the plateau phase of growth, not only do these human cells recover from sub-lethal radiation damage, but potentially lethal damage is repaired if the cells are allowed to remain in the stationary phase for some time after irradiation.
226 citations
Journal Article•
TL;DR: It was shown that cells whose proliferation was inhibited prior to exposure to MTX, either by lack of essential amino acids in the medium or by their having reached a stationary growth phase, were resistant to the cell killing action of the drug.
Abstract: Studies were carried out on L-cells in vitro realting the various Methotrexate (MTX)-induced perturbations of cellular metabolism to cell killing by the drug. In the tissue culture system used in these investigations, the inhibitory action of MTX could be completely reversed by the addition of thymidine and deoxyadenosine to the culture medium, indicating that all of the MTX-induced effects on cell proliferation and viability were due to the depletion of thymidylate and purines brought about by MTX disruption of folic acid metabolism. This permitted the resolution of the effects of these two inhibitions on cell killing. Results indicate clearly that cell killing results from the inhibition of thymidylate synthesis while the concurrent inhibition of purine synthesis tends to prevent efficient cell killing. Furthermore, it was shown that cells whose proliferation was inhibited prior to exposure to MTX, either by lack of essential amino acids in the medium or by their having reached a stationary growth phase, were resistant to the cell killing action of the drug. The significance of these results for chemotherapy is discussed.
138 citations
TL;DR: It is concluded that cyclic AMP plays a central role in the control of cell division in thymocyte populations and could be the intracellular mediator of the mitogenic actions of a wide variety of hormones on this type of cell.
127 citations
TL;DR: It is demonstrated that various regions of rat brain have different rates of cell division and that the entire pattern of cellular growth is regionally specific.
Abstract: Extract: The cellular growth patterns in whole brain, cerebrum, cerebellum, hippocampus, and brainstem were examined in rats between 6 and 22 days of age. When weight alone was measured, little difference was seen between the various regions; however, when cell number (DNA) or protein per cell (protein: DNA) was measured, regional differences became very striking. In the cerebellum, DNA content increased 8.5 fold between 6 and 17 days and subsequently tapered off. The protein: DNA ratio declined during this period. Although the increase in cell number in the cerebrum was only 2.5 fold, it continued until 21 days, at which time the experiment was terminated. After 10 days there was also an increase in the protein: DNA ratio. In the brainstem, there was a modest increase in cell number between 6 and 14 days. After 10 days the protein: DNA ratio increased 4 fold. In the hippocampus, there was a discrete increase in cell number only between 14 and 17 days. These data demonstrate the existence of distinct regional patterns of cellular growth during postnatal maturation of rat brain. Speculation: The brain, although often viewed as a discrete organ, is composed of a number of anatomically distinct regions that perform separate and unique functions. Previous data from this laboratory have shown that cell division ceases in whole rat brain by 21 days postnatally and in whole human brain by six months of age. This study demonstrates that various regions of rat brain have different rates of cell division and that the entire pattern of cellular growth is regionally specific. Since certain functions are regionally controlled, it is possible that the regional growth patterns described here have functional correlates. Alteration in the environment (nutrition) is known to affect the rate of cell division in whole brain. It is possible that environmental effects may be regionally specific. By studying the effects of environmental stimuli (anoxia or malnutrition) on regional growth patterns and correlating these effects with functional changes, it may be possible to relate cellular changes to functional deficits.
104 citations
TL;DR: Collagen proline hydroxylase activity could be stimulated independently of cell growth by rapidly concentrating the cells indicating an activation process associated with cell density.
87 citations
TL;DR: It is concluded that methods of determining growth rate by analysis of distributions of bacterial volumes do not yet have sufficient resolution to distinguish between a variety of alternative models for growth of bacteria.
81 citations
TL;DR: Adaptive balance between cell proliferation and sloughing, and thus migration rate, begins immediately after conventionalization of germfree animals as bacterial populations establish themselves throughout the gastrointestinal tract, and results in a doubling of the mucosal cell turnover after 8 days.
Abstract: The relationship between intestinal colonization and the small bowel mucosal cellular proliferation rate during conventionalization of the germfree mouse was examined. 16 mice were maintained under standard germfree conditions, and 54 others were conventionalized. Migration of the small bowel epithelial cells was followed by radioautography with administration of tritiated thymidine. Colonization was followed by qualitative and quantitative bacteriological fecal analyses. The percentages of the villi labeled (as determined by cell count) 24, 48, and 72 hr following thymidine administration showed immediate progression in the conventionalized animals from the germfree villus migration time (4 days) toward the conventional villus migration time (2 days). The epithelial migration rate of animals conventionalized for 8 days was comparable to that of conventional animals.
After conventionalization, aerobic and anaerobic organisms undergo a period of extensive multiplication; however, 72 hr later the number of these microorganisms cultured in the stool decrease and are similar to those recovered from normal animals. Coliforms and streptococci are recovered in large numbers only in the first days after conventionalization, while the Bacteroides are first recovered in significant numbers on the fifth day of conventionalization. Except for smaller numbers of Bacteroides , the bacterial populations in the stools of the conventionalized animals are qualitatively and quantitatively similar by the eighth day of conventionalization to those of true conventional mice.
Adaptive balance between cell proliferation and sloughing, and thus migration rate, begins immediately after conventionalization of germfree animals as bacterial populations establish themselves throughout the gastrointestinal tract, and results in a doubling of the mucosal cell turnover after 8 days. At this time both the small intestinal epithelial cell migration rate and the intestinal microflora are similar to those of conventional animals.
71 citations
TL;DR: In cultures of differentiating chicken embryo muscle cells there is a steep decline in DNA polymerase activity which closely parallels the time of rapid cell fusion and the formation of multinucleated myotubes.
Abstract: In cultures of differentiating chicken embryo muscle cells there is a steep decline in DNA polymerase activity which closely parallels the time of rapid cell fusion and the formation of multinucleated myotubes. The DNA polymerase activity remaining in the cultures is almost completely associated with single unfused cells. Cell fusion does not require a confluent culture and fusion capability appears to be severely reduced in the remaining single cells following an approximately ten hour time period during which the majority of fusion takes place. A model is presented to explain the observed kinetics of cell growth and cell fusion in vitro.
70 citations
TL;DR: The idea that the bacterial spore is a small cell, formed by an asymmetric cell division and enveloped by the larger sister cell, and both processes seem to be morphological expressions of unbalanced growth resulting from shift down growth conditions.
Abstract: This article reviews the idea that the bacterial spore is a small cell, formed by an asymmetric cell division and enveloped by the larger sister cell. Both processes seem to be morphological expressions of unbalanced growth resulting from shift down growth conditions.
67 citations
Journal Article•
TL;DR: The cell kinetics of two solid human tumors, invasive squamous carcinomas of the cervix, were studied by parenteral administration of tritiated thymidine followed by serial biopsy of the tumors at intervals for 24 hours, and subsequent radio-autographic analysis for mean grain counts and percent labeled mitoses.
Abstract: The cell kinetics of two solid human tumors, invasive squamous carcinomas of the cervix, were studied by parenteral administration of tritiated thymidine followed by serial biopsy of the tumors at intervals for 24 hours, and subsequent radio-autographic analysis for mean grain counts and percent labeled mitoses at these times.
In these two tumors, the majority of labeled cells were at the periphery of the tumor nodules (growth fraction of 41–53 percent). Tumor nodules appeared to grow by expansion from within, as newly formed cells migrated toward the centers of nodules. A significant proportion of interior cells (growth fraction of 17–20%) retained the capacity to divide, a function lost in the differentiation of normal epithelial cells, and thus were able to contribute to the total proliferative pool.
Cell cycle times were 15.5 and 14.3 hours, and DNA synthesis times were 11.8 and 9 hours. These times are not unlike those of normal mammalian cells, adding to the evidence that rapid tumor growth is not necessarily dependent upon rapid cell proliferation.
The observations that in these tumors: ( a ) the majority of dividing cells were at the periphery of nodules, ( b ) the growth fraction was reduced, i.e., maximum of 53 rather than 100 percent of basal cells were capable of dividing, and ( c ) periods of DNA synthesis were fairly long, points up the potential errors in estimating the cell cycle time from in vitro labeling studies.
The possibility that cells in the interior of tumor nodules may be arrested in mitosis is described, a factor which may prevent even faster growth than is already observed.
TL;DR: Investigation of the synthesis of 28S and 18S ribosomal RNA in human lymphocytes found that reduction of rRNA wastage is an early event in stimulation of lymphocyte growth, but that rRNA Wastage is not incompatible with cell growth under conditions of elevated rRNA synthesis.
TL;DR: The reaction of the bladder epithelium of mice, following stimulation with a carcinogen, 4‐ethylsulphonylnaphthalene‐1‐sulphonamide (ENS), was studied to find out the intensity and timing of the onset of cell division in the bladder tissue of individual animals.
Abstract: The reaction of the bladder epithelium of mice, following stimulation with a carcinogen, 4-ethylsulphonylnaphthalene-1-sulphonamide (ENS), was studied. A wave of cell division was induced in the resting epithelium, diploid and tetraploid cells being the main dividing elements; some of the high ploidy surface cells also underwent division. The cell cycle time for the diploid and tetraploid cells appeared to be identical. There was considerable variation in the intensity and timing of the onset of cell division in the bladder epithelium of individual animals. ENS caused severe damage to the surface cells of the bladder epithelium as indicated by increased lysosomes and the formation of large vacuoles.
TL;DR: It is concluded that chloroplast replication in Euglena gracilis is independent of nuclear and cellular replication, at least under B12 deficiency conditions.
Abstract: When Euglena gracilis is grown under vitamin B(12) deficiency conditions, the amount of protein and of chlorophyll per cell increase with decrease of B(12) in the medium and consequently in the cell. The increase in cell protein is proportional to and precedes an increase in the number of chloroplasts per cell. This replication of the chloroplasts under deficiency conditions is not accompanied by nuclear or cell division. It is concluded that chloroplast replication in Euglena gracilis is independent of nuclear and cellular replication, at least under B(12) deficiency conditions. We established a graph of the growth of Euglena under different concentrations of vitamin B(12) added to the growth medium, which permitted us to calculate that at least 22,000 molecules of vitamin B(12) per cell are required to give normal growth.
Journal Article•
TL;DR: Mammary carcinogenesis in the C3H mouse involves a complex interaction of viral, genetic, and hormonal factors, and this experimental model for breast cancer has been the subject of extensive investigation.
Abstract: Mammary carcinogenesis in the C3H mouse involves a complex interaction of viral, genetic, and hormonal factors, and this experimental model for breast cancer has been the subject of extensive investigation. Hormonal factors may be important both in the neoplastic transformation (6) and in the regulation of the rate of tumor growth (9). Previous studies demonstrated that cell proliferation in C3H mammary carcinoma expiants is stimulated by the addition of insulin to the synthetic medium, and the rate at which cells enter the DNA-synthetic (S) phase of the cell cycle may be further modified by estrogenic hormones (9). A protein has been isolated from the submaxillary salivary glands of mice which stimulates growth of epidermal cells (2). Under appropriate conditions the purified epidermal growth factor (EGF) causes increased numbers of epidermal cells to synthesize DNA (3). It may stimulate several types of rat epithelial cells to proliferate and has consequently been termed the \"epithelial growth factor\" (4). Although the
TL;DR: The data show that both DNA synthesis and mitosis require aerobic conditions and are energy-dependent and events prior to the initiation of these processes have relatively greater energy requirements than the rest of the mitotic cycle.
TL;DR: A direct relationship between the presence of anti-protease factors and growth of cells was shown with a wide variety of sera from different animals and man and the growth-promoting quality of serum was shown to be related to its titer against these enzymes.
TL;DR: The lipids of human diploid cell strain WI‐38 and of a line derived from it by SV40 transformation have been studied and the ability of the cells to synthesize lipids was assayed in a „resting”︁ cell system.
Abstract: The lipids of human diploid cell strain WI-38 and of a line derived from it by SV40 transformation have been studied. The lipid composition and fatty acid spectra of both resemble those reported for other tissue culture cells and human tissues. The lipids of the normal and transformed cells are similar except that there are decreases in the content of phospholipids and of arachidonic acid in the transformed cells. The ability of the cells to synthesize lipids was assayed in a „resting” cell system. Both cell types were able to incorporate labelled acetate into their component neutral lipids and phospholipids, but the rates observed were lower than that required for cell growth. Elevation in the rate of cholesterol synthesis was observed in the transformed cells. The data are discussed in relation to other reports in the literature on lipids and neoplasms.
TL;DR: Attempts are made to correlate chromosome puffing with specific cellular activities — cell growth, the sequential secretion of six cuticular layers (determined by electron microscopy), cuticle sclerotization and melanization, and eventual cell death.
Abstract: A description is given of the puffing sequences of the giant polytene chromosomes from the footpads of Sarcophaga bullata, from Day 3 to Day 12 of pupation at 25° C. The chromosome puffing patterns are seen to be very precise and to occur in orderly sequence with respect to general developmental events. Particular puffs appear or regress in a continuous, orderly sequence. A few puffs remain throughout adult development. Most are puffed for a limited time only. In several cases puffed regions appear to “move along” the chromosome, suggesting sequential activity of adjacent genetic loci. Attempts are made to correlate chromosome puffing with specific cellular activities — cell growth, the sequential secretion of six cuticular layers (determined by electron microscopy), cuticle sclerotization and melanization, and eventual cell death. Preliminary observation of thoracic trichogen cell chromosomes show interesting similarities and differences in puffing patterns, when compared with footpad sequences.
TL;DR: Experimental results are discussed in relation to the problem of the critical decision phase in the crypt, the possible role of esterase activity as a marker for cell differentiation and the functional implications of changes in the proliferative and maturing-cell compartments.
TL;DR: It is indicated that both growth hormone and insulin are required for optimum cell growth and overactivity of the sympathetic pathways may retard growth and produce effects that simulate hypopituitarism.
Abstract: Extract: This study explores changes in deoxyribonucleic acid (DNA), ribonucleic acid (RNA), protein, and water content of muscle, liver, and cerebrum in hypophysectomized rats and the effects of injecting growth hormone, insulin, or growth hormone with epinephrine conjointly over an eleven-day period. Male hypophysectomized rats, 26 to 49 days of age, fed an ad libitum diet were studied. At 38 days of age they were injected with insulin, 0.4 to 1.8 units per day, with bovine growth hormone (250 μUg/day) or with the same amount of growth hormone and epinephrine, 5 to 20 μUg/day, concomitantly, or were untreated until the 49th day of age. Control rats of the same age were either pair-fed to untreated hypophysectomized rats or given an ad libitum diet. Untreated hypophysectomized rats showed poor body weight gain per unit food intake and reduced skeletal growth. The nucleic acid and protein content of liver, muscle, and cerebrum was reduced when compared with controls of the same age. The ratio of protein: DNA (cell size) was increased for body size but reduced for age. Administration of insulin caused hypertrophy of liver cells and increased the protein content of liver, but did not affect muscle and cerebrum. DNA content of liver or cerebrum did not increase, and the gain in DNA content of muscle was not remarkable. There was a definite increase in RNA content of muscle, liver, and cerebrum and in the ratios of RNA: DNA and protein: DNA of liver. Injections of growth hormone caused an increase in DNA (cell number), RNA, and protein content in liver, muscle, and cerebrum. There was a reduction in the ratio of cytoplasm to nucleus. The protein increment was nullified by the injection of epinephrine in conjunction with growth hormone. DNA content of muscle and liver was increased, but not to the level produced by growth hormone alone. The increase in RNA content of liver, muscle, and cerebrum was again significant; the ratio of RNA: DNA increased only in liver. Caloric intake of untreated hypophysectomized rats and those treated with growth hormone or insulin was comparable. Rats injected with epinephrine showed a significant increase in caloric intake. The results indicate that insulin is involved with growth in cell size, while growth hormone is active with respect to the increase in cell number. Both hormones are required for optimal growth. Speculation: The present study indicates that both growth hormone and insulin are required for optimum cell growth. Epinephrine administration retards the increase in cell number that normally occurs in hypophysectomized rats receiving growth hormone. This suggests that overactivity of the sympathetic pathways may retard growth and produce effects that simulate hypopituitarism.
TL;DR: Cell volume distributions obtained with an electronic particle analyzer were used to study the changes in volume of individual cells in the absence of cell division and inhibitors of protein and RNA synthesis inhibited the cell volume growth of irradiated cells.
TL;DR: The rate of cell division was measured in cultures of Escherichia coli B/r strain after periods of partial or complete inhibition of deoxyribonucleic acid (DNA) synthesis, consistent with the idea that chromosome replication begins when an initiator complement of fixed size accumulated in the cell.
TL;DR: Fat cells from cold-acclimated rats are more sensitive to the lipolytic action of norepinephrine, independent of differences in cell size; the larger the cell the less sensitive it is.
Abstract: Adipose tissue in rats maintained at normal ambient temperature grows by a mixture of cell proliferation and lipid deposition in the early growth stage of the rat. In the mature rat, the tissue grows primarily by lipid deposition, mitotic activity being significantly decreased. When the rat is acclimated to 5 C, growth of adipose tissue is less than that of rats maintained at normal ambient temperature. Furthermore, growth of adipose tissue in the 5 C rat occurs through a mixture of cell proliferation and lipid deposition throughout the body weight range studied. The differences in tissue growth were taken into consideration in measuring the stimulatory effect of norepinephrine on lipolysis and reesterification of isolated fat cells. The results indicate that the cell size affects the lipolytic response; the larger the cell the less sensitive it is. Fat cells from cold-acclimated rats are more sensitive to the lipolytic action of norepinephrine, independent of differences in cell size. On the other hand, reesterification is not affected by cell size, nor by exposure of the rat to cold
TL;DR: The purpose of the experiments reported here was to determine what effects serum from hypercholesterolemic swine has on DNA synthesis and the division of cells in tissue culture as compared with the effects of serum from controls with "normal" cholesterol levels (NC).
Abstract: The most prominent feature of early atherosclerosis induced in swine by ingestion of cholesterol is the focal accumulation of smooth muscle cells (SMC) in arterial intimas that results from increased rates of DNA synthesis and cell division without corresponding increases in rates of cell death (Florentin et al ., 1968; Thomas et al ., 1968) . The nature of the interactions between the cells and their environment that account for the increases in unknown . The purpose of the experiments reported here was to determine what effects serum from hypercholesterolemic (HC) swine has on DNA synthesis and the division of cells in tissue culture as compared with the effects of serum from controls with \"normal\" cholesterol levels (NC) . A stimulatory effect occurred when HC serum was added at the 2070 level, with cell division rates increasing approximately twofold . The in vitro demonstration of an effect that parallels in vivo responses does not necessarily mean that the underlying cellular dynamics are the same . However, it seems reasonable to accept as a working hypothesis that the dynamics are similar, and to exploit the in vitro approach presented herein, with the expectation that this approach will provide insight into cellular mechanisms involved in cholesterol-induced atherosclerosis .
TL;DR: This chapter discusses the four different types of animal cells in terms of cytoplasmic regulation of nuclear behavior during the cell cycle, as in Pelomyxa, Opalina, multinucleate cells, and sometimes not, where DNA synthesis and nuclear division are both asynchronous.
Abstract: Publisher Summary This chapter discusses the four different types of animal cells in terms of cytoplasmic regulation of nuclear behavior during the cell cycle. The extent of cytoplasmic control over nuclear events of cell reproduction is reviewed. Nuclear transplantation studies for Stentor and the Xenopus egg, combined with radioautography, show extensive cytoplasmic regulation of nuclear behavior during cell division and of nucleic acid synthesis. The mechanisms for timing the cell cycle are located in the cytoplasm, which assume responsibility for keeping the nuclear events “in step” with the cytoplasmic ones. The cell cycle is timed by changing structural relationships within the cytoplasmic cortical fibrillar system. In multinucleate cells, where no apparent need exists for coordination of nuclear and cytoplasmic events, nuclear reproduction is regulated by the cytoplasm, as in Pelomyxa , and sometimes not, as in Opalina , where DNA synthesis and nuclear division are both asynchronous. The source of the cytoplasmic signals regulating nuclear reproduction is also investigated.
TL;DR: These findings suggest that precocious development of UDP-glucuronyltransferase activity in chick embryo liver is due, not to incidents of culture, but to removal from the embryonic environment, and supporting this, chick embryo Liver grafted to the chorioallantoic membrane does not develop UDP- GLT activity until subsequently transferred to an in vitro cell culture system.
Abstract: Very young (5-day-old) chick embryo livers during organ culture on rafts over a chemically defined nutrient medium precociously develop, from zero, adult levels of UDP-glucuronyltransferase activity. Induction of enzyme does not require DNA synthesis or mitosis, or exposure to hormones, serum, or tissue extracts. Thus, this functional differentiation of embryo liver is apparently not dependent on cell proliferation or on extrinsic substances other than simple nutrients.
UDP-glucuronyltransferase activity develops rapidly also in embryo liver cells cultured as monolayers or aggregates; specific activity of enzyme on a protein basis increases at the same rate in cells undergoing widely different rates of cell division, and net protein synthesis.
These findings suggest that precocious development of UDP-glucuronyltransferase activity in chick embryo liver is due, not to incidents of culture, but to removal from the embryonic environment. Supporting this, chick embryo liver grafted to the chorioallantoic membrane does not develop UDP-glucuronyltransferase activity until subsequently transferred to an in vitro cell culture system.
TL;DR: The cell population of the normal adult rat thyroid gland, a closed population, shows very little proliferation as measured by sequential changes in thyroid weight, cell density, chemical DNA and RNA and by total uptake of tritiated thymidine into cell DNA or by cell-labelling indices.
Abstract: SummaryThe cell population of the normal adult rat thyroid gland, a closed population, shows very little proliferation as measured by sequential changes in thyroid weight, cell density, chemical DNA and RNA and by total uptake of tritiated thymidine (3H-T) into cell DNA or by cell-labelling indices (L.I.). In contrast, administration of a continuous goitrogenic challenge (0·1 per cent methylthiouracil as drinking fluid and a low iodine diet) induces, after a lag phase of 2 days, a 2–3-fold increase in thyroid weight, the maximum weight being attained within 28 days of the goitrogenic challenge. During thyroid growth the cell density falls about 10 per cent; chemical DNA rises with gland weight but slightly less than chemical RNA; and both the uptake of 3H-T and L.I. parallel the rate of change of DNA content.Doses of 100, 500 or 1000 rads x-rays given to the normal rat thyroid produce latent cell damage; there is an impairment of weight increase during a subsequent goitrogenic challenge, and this is relat...
TL;DR: In the presence of 10-2 M hydroxyurea cell division is prevented but cell growth continues, and the rate of cell growth varies within the apex, depending on the location of the cell.
Abstract: In the presence of 10-2 M hydroxyurea cell division is prevented but cell growth continues. The rate of cell growth varies within the apex, depending on the location of the cell. The rate of growth is low in the quiescent centre and non-dividing region of the root cap but higher elsewhere.