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Biomedical subjects

J F Whitfield

Publications and source records attributed to J F Whitfield.

At least 199 records · Page 11Linked to original sources
PubMed1976

A possible involvement polyamines in the initiation of DNA synthesis by human WI-38 and mouse BALB/3T3 cells.

Changing the medium, or adding fresh serum, induces a large proportion of the proliferatively quiescent cells in confluent monolayers of human WI-38 and mouse BALB/3T3 cells to initiate a growth-division cycle. Exposure at the time of the medium change or serum addition to MGBG (methyl glyoxal bis [guanylhydrazone]), an inhibitor of spermidine and spermine synthesis and function, reduces or stops the subsequent flow of cells into the DNA-synthetic phase, without grossly affecting RNA synthesis. Mediation of MGBG action by an actual or functional shortage of spermidine or spermine (but not putrescine), and consequently an involvement of these polyamines in DNA synthesis, is strongly suggested by the reduction of the inhibitor's effectiveness by a brief (1-hour), early prereplicative exposure of the treated cells to exogenous spermidine and spermine (but not putrescine).

Cell Line↗
PubMed1976

The different roles of serum and calcium in the control of proliferation of BALB/c 3T3 mouse cells.

Proliferatively inactive BALB/c 3T3 mouse cells in dense cultures initiate a growth-division cycle upon exposure to fresh calf serum in a low-calcium (0.01 mM) medium. If these calcium-deprived cells are not supplied with calcium sometime during the first 10 hours after serum stimulation, they will rapidly return to a proliferatively inactive state without initiating DNA synthesis. The prereplicative development of such stimulated calcium-deprived cells appears to stop at an advanced stage, because addition of calcium as late as 10 hours after serum exposure rapidly initiates DNA synthesis, and enables the culture's DNA-synthetic activity subsequently to reach its peak value at the same time as in control cultures.

Blood↗
PubMed1976

The different actions of normal and supranormal calcium concentrations on the proliferation of BALB/c 3T3 mouse cells.

In the presence of a normal (1.25 to 1.80 mM) calcium concentration, addition of fresh bovine calf serum or completely changing the medium induces proliferatively quiescent BALB/c 3T3 mouse cells in dense cultures to start a growth division cycle and initiate DNA synthesis about 12 hr later. Fresh, low-calcium (0.02 mM physiologically available) medium also causes cells to start a growth-division cycle. Howver, the development of such stimulated, calcium-deprived cells tops just before the expected time of initiation of DNA synthesis, which can then be rapidly induced by restoration of the normal calcium concentration. Simply raising the calcium concentration to nonphysiologically high levels (without otherwise altering the medium) can mimic the action of fresh serum or fresh whole medium by inducing some of the cells in proliferatively quiescent confluent concluent cultures to start a growth-division cycle and initiate DNA synthesis 22 hr later.

Calcium↗
PubMed1976

The positive control of cell proliferation by the interplay on calcium ions and cyclic nucleotides. A review.

Calcium, cyclic AMP, and cyclic GMP do not seem to be involved in proliferative activation of postmitotic differentiated cells. Instead, they are intracycle regulators, and we propose the following working model of their control of the initiation of DNA synthesis. While a role for cyclic GMP cannot yet be defined, a brief postmitotic burst of its synthesis might serve to prevent certain activated cells (e.g. 3T3 mouse cells) from being diverted into a nonproliferating (but still activated) G0 state (Figs. 1 and 17). In a latter part of the G1 phase, something happens to stimulate briefly the synthesis of cyclic AMP which, in turn, drives calcium ions from the mitochondria into the cytosol to activate newly synthesized thymidylate synthetase (or other primed enzymic assemblies) (Fig. 1). Having "turned on" their target enzymes, the accumulated cyclic AMP is destroyed and the excess calcium ions are reaccumulated by the mitochondria to avoid interfering with succeeding reactions. This model predicts that persistent changes in cyclic AMP metabolism and the respiration-linked, calcium-accumulating (ion-buffering) activity of mitochondria may be responsible for the sustained growth of tumors.

Acetylcholine↗
PubMed1976

Regulation by calcium of the proliferation of heart cells from young adult rats.

Cells of primary and secondary cultures of rat heart ventricle were grown in a medium supplemented with homologous plasma to avoid the non-specific proliferogenic effects of foreign sera. Specific chelation of calcium from the medium arrested the cells' progression through their cycle at the G1 phase. A permanent or brief restoration of the extracellular calcium level (48 hr later) was followed, after a 5 to 6 hr delay, by a burst of DNA synthesis, and the resumption of mitotic activity.

Animals↗
PubMed1976

Different calcium requirements for proliferation of conditionally and unconditionally tumorigenic mouse cells.

Conditionally tumorigenic BALB/3T3 mouse cells (which produce tumors in BALB/c mice only under special conditions) cannot sustain DNA synthesis and consequently stop proliferating in media containing low concentrations (0-0.02 mM) of physiologically available calcium. By contrast, cells that have been neoplastically transformed (tumorigenic in mice without special assistance) in vitro by different oncogens, can sustain DNA synthesis and proliferate in such calcium-deficient media. The possible importance for tumor growth of an ability to withstand calcium deprivation is examined. It is suggested that this property may prove to be a reliable indicator of neoplastic transformation.

Calcium↗
PubMed1976

Alteration by malignant transformation of the calcium requirements for cell proliferation in vitro.

Cells from the thigh muscles of normal fetal rats proliferated rapidly and indefinitely in a medium containing adult rat "plasma" and a normal free-calcium concentration, but they could not proliferate in calcium-deficient plasma medium. As the animals grew older, the cells became increasingly less able to proliferate even in normal (high-calcium) plasma medium, though they retained the potential to proliferate in a more conventional medium containing fetal bovine serum. By contrast, neoplastic adult cells from malignant rhabdomyosarcomas (induced by Ni3S2) proliferated rapidly and indefinitely in both normal and low-calcium plasma medium

Animals↗
PubMed1975

Acetylcholine-induced initiation of thymic lymphoblast DNA synthesis and proliferation.

Low (5 times 10-9 M to 10-7 M) acetylcholine concentrations cause a calcium-independent stimulation of the initiation of DNA synthesis and proliferation of lymphoblasts which are part of rat thymocyte populations suspended in vitro. A much higher (5 times 10-5 M) acetylcholine concentration also stimulates lymphoblast DNA synthesis and proliferation, but this action is calcium-dependent. This proliferogenic response to acetylcholine is however not clearly mediated by either cyclic GMP or cyclic AMP.

Acetylcholine↗
PubMed1975

The control of liver regeneration by parathyroid hormone and calcium.

Following partial hepatectomy in rats, there were two bursts of hepatocyte DNA-synthetic and mitotic activity which were produced by two subpopulations having different rates of (nearly synchronous) proliferative development. Only about 50% of the cells in both subpopulations could initiate DNA synthesis and enter mitosis when exposed to the hypocalcemic conditions in the parathyroprivic rat for 24 hours before partial hepatectomy. The proliferatively incompetent hepatocytes in these hypocalcemic rats could be induced to initiate their DNA synthetic and mitotic activity by an intraperitoneal injection of the calcium-mobilizing parathyroid hormone (50 USP units/100 g) as late as 12 hours after partial hepatectomy. Single intraperitoneal injections of calcium (0.25 mg/100 g) could also restore the proliferative competence of these hepatocytes, but only when injected at specific periods following partial hepatectomy. The injection of calcium 12 to 15 hours after partial hepatectomy induced hepatocytes in the first subpopulation to finish their development and enter mitosis, but did not affect the second, more slowly developing, subpopulation. Calcium had to be injected 25 hours after partial hepatectomy to stimulate proliferation in this second subpopulation. These data suggest that the hepatocytes which became proliferatively incompetent by prolonged exposure to a hypocalcemic environment are proliferatively activated by partial hepatectomy, but their proliferative development stops at a calcium-dependent stage near the end of the pre-replicative phase of development.

Animals↗
PubMed1973

Roles of calcium, serum, plasma, and folic acid in the control of proliferation of normal and Rous sarcoma virus-infected chicken fibroblasts.

In a culture medium of pH 7.4 and a folic acid concentration of 100 mug/liter that contains 5% heat-inactivated chicken plasma rather than serum, the rate of proliferation of normal chicken fibroblasts is determined by the concentration of calcium. Proliferation, rapid when the calcium concentration is physiological, decreases when the calcium concentration is reduced. At a very low calcium concentration, in this culture medium, normal fibroblasts are maintained without proliferation, whereas those infected with Rous sarcoma virus proliferate rapidly. This proliferative inactivity of normal fibroblasts does not involve contact-inhibition, since the effect is observed at low, as well as higher, culture densities. When a physiological amount of calcium is added to cultures of normal fibroblasts that have been maintained in very low calcium-plasma medium for 3 days, labeled thymidine uptake and protein synthesis are strongly stimulated, and cell division follows. The use of heat-inactivated chicken serum, instead of plasma, in this medium appears to strongly sensitize normal fibroblasts to the mitogenic action of calcium. In a plasma-containing culture medium of physiological calcium concentration and a folate concentration of 5 mug/liter, neither normal nor Rous sarcoma virus-infected fibroblasts proliferate to an appreciable extent. The use of serum, however, instead of plasma results in rapid proliferation of both normal and infected cells, as does increase in the folate concentration of the plasma-containing medium to 100 mug/liter.The fact that while normal fibroblasts are maintained without proliferation in low calcium-plasma medium, Rous sarcoma virus-infected fibroblasts proliferate rapidly, indicates that the effect of calcium is regulatory rather than permissive. These results suggest that the proliferation of normal fibroblasts is initiated by a cellular function involving calcium, and that the autonomous proliferation of the neoplastic fibroblasts results either from increased calcium uptake or from an alteration or a hypass of that function. The results also suggest that serum contains a mitogenic factor(s) not present in plasma, possibly a "wound hormone" for fibroblasts.

Animals↗