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R Rowley

Publications and source records attributed to R Rowley.

33 records · Page 2Linked to original sources
PubMed1985

Is G2-arrest an active cellular response to irradiation?

Protein synthesis is normally required for G2-cell progression and for recovery from radiation-induced G2-arrest. In the presence of 5 mM caffeine this requirement is alleviated, indicating that the mechanism responsible for G2 cell progression actually remains intact in irradiated or protein synthesis inhibitor-treated cells. It is suggested that both radiation and cycloheximide-induced G2-arrest are not, therefore, passive consequences of cellular defects, but are rather, active cellular responses to the state of cellular integrity, implying the existence of G2 cell progression controls.

Animals↗
PubMed1985

Cell cycle age dependence for radiation-induced G2 arrest: evidence for time-dependent repair.

Exponentially growing eucaryotic cells, irradiated in interphase, are delayed in progression to mitosis chiefly by arrest in G2. The sensitivity of Chinese hamster ovary cells to G2-arrest induction by X rays increases through the cell cycle, up to the X-ray transition point (TP) in G2. This age response can be explained by cell cycle age-dependent changes in susceptibility of the target(s) for G2 arrest and/or by changes in capability for postirradiation recovery from G2-arrest damage. Discrimination between sensitivity changes and repair phenomena is possible only if the level of G2-arrest-causing damage sustained by a cell at the time of irradiation and the level ultimately expressed as arrest can be determined. The ability of caffeine to ameliorate radiation-induced G2 arrest, while inhibiting repair of G2-arrest-causing damage makes such an analysis possible. CHO cell monolayers were irradiated (1.5 Gy), then exposed to 5 mM caffeine for periods of 0-10 hr. Cell progression was monitored by the mitotic cell selection procedure. In the presence of caffeine, progression of irradiated cells was relatively unperturbed, but on caffeine removal, G2 arrest was expressed. The duration of G2 arrest was independent of the length of the prior caffeine exposure and, since cells of all ages were ultimately examined, the duration of arrest was also independent of cell cycle age at the time of irradiation. This finding indicates that the target for G2-arrest induction is present throughout the cell cycle and that the level of G2-arrest damage incurred is initially constant for all cell cycle phases. The data are consistent with the existence of a time-dependent recovery mechanism to explain the age dependence for radiation induction of G2 arrest.

Animals↗
PubMed1984

Effect of caffeine on radiation-induced mitotic delay: delayed expression of G2 arrest.

In the presence of 5 mM caffeine, irradiated (1.5 Gy) S and G2 cells progressed to mitosis in register and without arrest in G2. Caffeine (5 mM) markedly reduced mitotic delay even after radiation doses up to 20 Gy. When caffeine was removed from irradiated (1.5 Gy) and caffeine-treated cells, a period of G2 arrest followed, similar in length to that produced by radiation alone. The arrest expressed was independent of the duration of the caffeine treatment for exposures up to 3 hr. The similarity of the response to the cited effects of caffeine on S-phase delay suggests a common basis for delay induction in S and G2 phases.

Animals↗
PubMed1983

In vivo and in vitro binding of iodinated monoclonal antibody A2B5 to RIN insulinoma cells.

Monoclonal antibody A2B5 reacts with the cell surface of a series of amine precursor uptake decarboxylation (APUD) cells and their tumors in many vertebrate species including chicken, rat, mouse, and man. We have studied the in vivo and in vitro binding of iodinated monoclonal antibody A2B5 to rat insulinoma cells. In vitro, radiolabeled A2B5 binds specifically to RINm5F insulinoma cells and the binding of 125I-A2B5 is inhibited by unlabeled A2B5 or a ganglioside extract of RINm5F cells. In vivo, scintigrams taken Day 0 to Day 5 after injection of 131I-labeled A2B5 showed a striking localization of 131I-A2B5 in transplanted RIN tumors grown in syngeneic rats. Other control radiolabeled monoclonal antibodies did not concentrate in the tumors. 131I-labeled A2B5 did not concentrate in other transplantable tumors (colon adenocarcinoma, osteosarcoma, renal cell carcinoma, and bladder transitional cell carcinoma) grown in nude mice. The tumor/blood ratio detected 5 days after antibody injection, was approximately two to 12 times higher in the insulinoma compared to other organs and only in the insulinoma did 131I-A2B5 show a higher concentration than control antibody 125I-P3X63.

Adenoma, Islet Cell↗
PubMed1982

An investigation of the association between anterior open-bite and amelogenesis imperfecta.

Fifty subjects with amelogenesis imperfecta were investigated clinically and with cephalometric radiography in order to determine the prevalence and nature of the anterior open-bite, which has been reported in association with these enamel defects. Anterior open-bite occurred in 24 percent of the subjects and was always associated with a severe discrepancy in the vertical relationship of the jaws. This vertical dysgnathia also occurred in a further 20 percent who did not have anterior open-bite. It is suggested that the frequent association of anterior open-bite and amelogenesis imperfecta is caused by a genetically determined anomaly of craniofacial development, rather than by local factors influencing alveolar growth.

Adolescent↗
PubMed1982

In vivo tumour-cell proliferation after adriamycin treatment.

Adriamycin (10 mg/kg) administered s.c. to male ACI rats bearing Hepatoma H-4-II-E caused a 9-day delay in tumour growth but no changes in the clonogenic fraction of the tumour were detectable by in vitro assay at any time after treatment. There is no significant decrease in the yield of cells on enzymatic dissociation of the tumour nor a reduction in mg DNA/g tumour that might indicate a decrease in tumour cellularity. Mitotic and labelling indices and [3H]dT uptake into DNA remain essentially unchanged, relative to age-equivalent controls, but are slightly lower than in controls of equal weight. The reliability of the clonogenic assay and possible mechanisms by which Adriamycin delays tumour growth are discussed.

Animals↗
PubMed1982

Modification of radiation-induced division delay by caffeine analogues and dibutyryl cyclic AMP.

The mitotic selection procedure for cell cycle analysis was utilized to investigate the concentration-dependent modification of radiation-induced division delay in Chinese hamster ovary (CHO) cells by methyl xanthines (caffeine, theophylline, and theobromine) and by dibutyryl cyclic AMP. The methyl xanthines (concentrations from 0.5 to 1000 micrograms/ml) all reduced radiation-induced division delay with the effect being linear between approximately 100 and 1000 micrograms/ml. After doses of 100-300 rad, delay was reduced by 75, 94 or 83 per cent at 1000 micrograms/ml for each drug, respectively. However, the addition of dibutyryl cyclic AMP had an opposite effect: radiation-induced delay was increased by the concentration range of 0.3 to 300 micrograms/ml. These results indicate that in mammalian cells the control of cell cycle progression and the modification of radiation-induced division delay are not simply related to intracellular levels of cyclic AMP. Rather, there appear to be at least two competing mechanisms which are differentially affected by caffeine analogues or by direct addition of dibutyryl cyclic AMP. The direct effect of caffeine and the methyl xanthines on membrane calcium permeability is considered.

Animals↗
PubMed1980

Response and recovery kinetics of a solid tumour after irradiation.

The effects of local tumour radiation over the dose range 7.5-30 Gy on the growth and cell kinetics of rat hepatoma H-4-II-E have been investigated. A plot of growth delays against log surviving fraction was linear below a fraction of 0.03, but failed to extrapolate to the origin. Following a single dose of 15 Gy to the tumour, DNA-precursor incorporation, labelling and mitotic indices were depressed for 7 days. Tumour cellularity, measured as DNA/g tumour, was reduced and the rate of increase of total clonogenic cells slower than after complete tumour recovery. From Day 7 to Day 9 all indices of proliferation recovered to about control levels, clonogenic cell numbers increased more rapidly and tumour cellularity was restored. Repopulation of the tumour therefore appeared to take place mainly after Day 7. Incorporation of [3H]-TdR into tumour DNA reached twice the control values on Day 9. The rate of tumour growth accelerated after the initial decrease, and maximum tumour growth rate was also twice the control values on Day 13. Accelerated growth rates in irradiated tumours, above those of control tumours, occurred 10-16 days after treatment. The effectiveness of sequential therapy may therefore be improved if given during this period of of accelerated tumour growth.

Animals↗
PubMed1980

Erythrocyte polyamine levels in rats with H4IIE hepatomas before and after radiation treatment.

The concentration of the polyamines, spermidine and spermine associated with the erythrocytes of rats with H-4-II-E hepatomas increased with tumor growth. Following radiation therapy the erythrocyte spermidine and spermine levels decreased by 63 and 47% respectively. Six days after radiation treatment the erythrocyte polyamines had increased to the pre-treatment elevated levels. These data suggest that erythrocyte polyamine levels may be useful in assessing the response to therapy and in detecting the continued growth of the tumor in patients with malignant disease.

Animals↗
PubMedDate not supplied

Regulation of the G2-mitosis transition.

The cell cycle is regulated by pathways composed of a dependent series of steps, by timers, and by checkpoint controls which ensure the completion of one event before the initiation of another. This review focuses on the regulation of the initiation of mitosis, with particular emphasis on the regulation of p34cdc2 activity at this point in the cell cycle. The review draws on data from various organisms, but strongly emphasizes the genetic framework as seen in the fission yeast Schizosaccharomyces pombe and the biology and biochemistry of maturation promoting factor in frog oocytes. An attempt is made to include all known genes and proteins where a link can be made to the initiation event. The nutritional size control and its major known controlling elements, the wee1/mik1 protein kinases, and cdc25 protein tyrosine phosphatase are considered in detail along with their regulation. In addition, the checkpoint control pathways which mediate G2 delay in response to failure of DNA replication or DNA damage are examined.

Animals↗
PubMedDate not supplied

In vitro response to hyperthermia or X-irradiation of diploid and tetraploid RIF-1 cells separated by centrifugal elutriation.

The RIF-1 cell line at the University of Utah is comprised of approximately 65 per cent diploid and 35 per cent tetraploid cells. Because sensitivity to heat cell killing has been shown to be ploidy dependent (Lucke-Huhle 1978), the responses of these subpopulations were examined independently. Diploid and tetraploid cells were separated from stock in vitro cultures by centrifugal elutriation and maintained entirely in vitro. No influence of ploidy on Do or Dq of heat dose survival curves could be detected. Neither did ploidy affect sensitivity to X-irradiation. However, separation of the diploid and tetraploid subpopulations was imperfect. The ratio of diploid to tetraploid cells in the separated and parent (mixed ploidy) lines was therefore monitored at each passage. Tetraploid contamination of the diploid cell subline was undetectable at the time of separation but regrew to 35 per cent by 40 days after separation. Diploid contamination of the tetraploid subline was initially less than 5 per cent and remained quite low until it became undetectable at 74 days. Differences in regrowth of the contaminating subline could not be accounted for by differences in plating efficiency or doubling time, but might result from subpopulation interactions. If so, such phenomena should be considered when using ploidy-dependent cytotoxic treatments.

Cell Line↗
PubMedDate not supplied

Influence of limb restraint on the thermal response of bone marrow CFU-GM heated in situ.

The method used to restrain anaesthetized (sodium pentobarbital) mice for in situ heating of tibial marrow affects the survival response of CFU-GM. Three methods of limb restraint, in addition to ischaemia induced by tourniquet, were examined for their relative effect on the thermal response of CFU-GM. The three methods of restraint were to secure only the toes with suture material to a submersion post in the water bath, to tape the foot, or to tape the leg. Temperatures in the lumen of the tibia were measured with a 100 micron (tip diameter) microthermocouple during representative experimental conditions. After heating in situ, bone marrow was extruded and CFU-GM cultured in standard soft agar conditions in lung-conditioned medium. The most restrictive restraining method, i.e. taping the leg, produced the greatest thermal response among the three restraining methods examined. The D0 (+/- 95% CI) of the 42 degrees C survival curve for CFU-GM was 22 +/- 4, 46 +/- 8, or 94 +/- 53 min for restraint of leg, foot, or toes, respectively. Survival reached a plateau by 100 min of heating indicative of the development of thermotolerance. The D0 of the 44 degrees C survival curve was 3 +/- 1, 6 +/- 2 and 16 +/- 6 min for restraint of leg, foot, or toes respectively. Ischaemia produced the most pronounced effect on the thermal response of tibial CFU-GM with D0 values of 2 +/- 1 or 3.6 +/- 1.5 min after exposure to 44 degrees C or 42 degrees C, respectively. The method of limb restraint affects the thermal sensitivity of CFU-GM most probably by blood flow obstruction and resultant pH decrease. Thus, precautions must be taken to ensure that limb restriction does not introduce artifacts in the hyperthermia response of normal tissues or tumours during heating in situ.

Animals↗