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D L Dewey

Publications and source records attributed to D L Dewey.

At least 19 recordsLinked to original sources
PubMed1988

The effect of oxygen on the delay in the initiation of DNA synthesis after irradiation.

The effect of oxygen on cell cycle delay by low doses of radiation on synchronized Harding Passey melanoma cells has been studied. Cells were irradiated 5 h after subculturing into fresh medium, and the delay before the start of S was measured. DNA synthesis was measured by frequent pulse labeling of the cells with radioactive thymidine to obtain the S-phase profile. The amount by which the irradiated cells S-phase profile had to be moved in time so that both the ascending and descending portions of the first S phase overlayed that of the controls was used as a measure of the delay. The magnitude of the delay was exponentially related to radiation dose and the effect of irradiating in the absence of oxygen was a dose multiplying factor of 2.5. This was similar to the oxygen effect on survival for cells irradiated under the same conditions.

Animals↗
PubMed1987

Cycle reset in a melanoma cell line caused by cooling.

When cells in culture are released from G0 into cycle by diluting into fresh medium there is a delay of many hours before they re-enter the cycle and start DNA synthesis. A mouse melanoma cell line designated HP2 has been used to investigate the effects of non-standard temperatures between the time of plating and DNA synthesis. When the cells were incubated in a 5% CO2 box at 8 degrees C for periods during the G0-G1 transition there was an extra delay before the start of S, approximately equal to the time that the cells were held at 8 degrees C and independent of the time when the cold pulse was administered. When the cells were cooled to 25 degrees C the delay was longer than the time for which the cells had been kept at 25 degrees C, and this extra delay was also dependent on the point in G0-G1 when the cells were cooled, as though the cells could be reset to an earlier time by this treatment. It is suggested that a labile substance required for progression is destroyed faster than it is made at 25 degrees C but at 8 degrees C the rate of destruction is very low. Another phenomenon noted during these cooling experiments was that the peak height of the S phase profile, as measured by frequent pulse-thymidine incorporation experiments, was substantially higher for cells which had been cooled at a later stage in the G0-G1 transition, even though the overall times at 37 degrees C and at the colder temperature were identical. By varying the temperature of the cold pulse it was possible to separate the change in the peak height and the delay as separate entities.

Animals↗
PubMed1984

Delay in entry into S phase after heat shock.

Synchronized cells of the Harding Passey melanoma grown in culture were given a heat shock treatment of 44 degrees C for 36 min. Thymidine incorporation was measured at frequent intervals after heat shock to determine the time of onset of the next DNA synthetic period. If the heat shock was given at the end of G1, the following S was delayed by 20 hr. Heating at other times in the cell cycle resulted in an even longer interval before the onset of S. The end of G1 was also the most resistant to hyperthermic killing and to the effect of heat on the magnitude of thymidine incorporation in the following S. Heating the cells a second time did not repeat the effect of the first treatment unless the second heat shock treatment was at a considerably higher temperature. Thus thermotolerance to heat shock killing also applies to cell-cycle delay.

Animals↗
PubMed1983

Differential toxicity of methylglyoxal-bis [guanylhydrazone].

The toxicity to cultured cells of the cancer chemotherapeutic agent methylglyoxal-bis[guanylhydrazone] (MGBG) varies considerably between different cell lines and is always more toxic in the absence of exogenous polyamine. We have looked at the relative MGBG toxicity of two different murine melanoma tumour cell lines (Harding-Passey and Cloudman) and normal murine fibroblasts, and found wide variation with no correlation in sensitivity to MGBG between tumour and normal cells. High sensitivity to MGBG may be associated with high transport across the cell membrane.

Animals↗
PubMed1981

Hog kidney diamine oxidase conversion of biogenic diamines to inhibitors of cell proliferation.

Hog kidney diamine oxidase (DAO) interacted with 1,3-diaminopropane, putrescine and cadaverine to arrest proliferation of cultured mammalian cells. The byproducts of DAO-substrate interaction, H2O2 and NH4+ are themselves cytotoxic but were apparently not responsible for any significant antiproliferative effect in the experimental system. DAO is known to react with putrescine to generate labile 4-aminobutyraldehyde. This primary product was compatible with a compound (radio-labelled) separated from DAO-putrescine reactive mixtures by ion-exchange chromatography. Its rate of generation, level attained and lability (half-life, 2 hr) in culture simulated conditions were measured. Circumstantial evidence suggested that the amine aldehyde products of diamine oxidation had a potent antiproliferative effect on cells.

Aldehydes↗
PubMed1980

Inhibition of proliferation of cultured cells by polyamine and cysteine interaction.

Both L-cysteine and spermidine oxidation inhibited the proliferation of cultured cells when these reagents were added in low concentrations. Higher concentrations (above 1 mM) of cysteine were not cytotoxic. Furthermore, high concentrations of L-cysteine partially protected against spermidine oxidation toxicity. D-cysteine on its own behaved exactly the same as an equimolar concentration of L-cysteine, but instead of protecting against the effects of spermidine oxidation, the inhibition was enhanced. A possible mechanism for the interaction is discussed.

Animals↗
PubMed1980

Oxygen-dependent free radicals in spermine oxidation cytostatis and chemiluminescence and the role of superoxide dismutase.

Spermine interacted with serum polyamine oxidase (PAO) to arrest proliferation of cultured Bri8 lymphocytes. Arrest was independent of catalase activity and was not directly due to an H(2)O(2) byproduct. Arrest was averted by 3-hydroxybenzyloxyamine, which inactivates the pyridoxal co-factor of PAO. The oxidation of spermine in the presence of different concentrations of PAO was non-linear, which implied complex intermediate events for conversion of spermine to labile di-oxidized spermine (N,N'-bis(3-propionaldehyde)-1,4-butanediamine) with, perhaps, overall generation of free radicals (O(2) (-·) and ·OH) which are damaging to cells. Exogenous free radicals were apparently neither direct participants in cytostasis, nor in the chemiluminescence demonstrable for spermine oxidation. Thiourea, an ·OH scavenger, protected against both proliferation arrest and luminescence. Many other powerful ·OH scavengers, however, were ineffective. Though reaction mixtures reduced ferricytochrome c initially, reduction was not inhibited by superoxide dismutase (SOD) which indicated that the anion O(2) (-·) had not been generated. The powerful reducing capability of di-oxidized spermine itself could have competed against any O(2) (-·) for ferricytochrome c reduction. Nevertheless, O(2) (-·) was generated during further PAO conversion and/or auto-oxidation of di-oxidized spermine. Curiously, addition of SOD to destroy presumptive O(2) (-·) variably potentiated cytotoxicity. Blockage of any anion channels in the cell plasma membrane by stilbene derivatives did not influence cytotoxicity. Thus, findings support our previous evidence that cationic di-oxidized spermine is a potent G(1) inhibitor of cell proliferation. The possibility of intracellular free-radical and thiol involvement is discussed.

Catalase↗
PubMed1979

Tumour uptake of thallium-201 chloride.

The uptake of 201Tl-chloride in tumours has recently been investigated in several authors' laboratories. We are reporting studies on the uptake in malignant melanoma in mice. Generally, we confirm the published data qualitatively in finding higher uptake in tumour than in muscles. We confirm the rapid blood clearance and high kidney concentration, but we did not measure the myocardial uptake. We observed the concentrations in kidney muscle and tumour to rise during the first four hours while that in the liver fell from one hour onwards. We did not observe markedly higher uptake in melanin rich tumour than in other tumours.

Animals↗
PubMed1979

Methyl glyoxal bis guanylhydrazone abolition of the toxic action of spermidine on cells in culture.

Spermidine inhibits many cells in culture because amine oxidase in the serum converts spermidine to toxic products. Methyl glyoxal bis guanylhydrazone (Methyl GAG) inhibits cells in culture because it is a specific inhibitor of S-adenosylmethionine decarboxylase, preventing the conversion of putrescine to spermidine. When both spermidine and methyl GAG were added together, no inhibition was observed. The effect could be explained by the finding that methyl GAG was a powerful non-competitive inhibitor of the enzymatic oxidation of spermidine to acrolein.

Acrolein↗
PubMed1979

Evidence for serum binding of oxidized spermine and its potent G1-phase inhibition of cell proliferation.

Serum polyamine oxidase (EC 1.4.3.4) is known to react in vitro with radio-labelled spermine4+ to produce di-oxidized spermine which must incorporate the label. Di-oxidized spermine was compatible with a radio-labelled compound2+ separated from the reaction mixture by ion-exchange chromatography. The compound was measured and had a half-life of about 2.3 h in tissue culture medium. It also rapidly and tightly bound to an unidentified serum component (gel-filtration chromatography indicated a complex of mol. wt 70,000) so that dissociation required treatment with strong acid (10N HCl). Findings suggest that the di-oxidized spermine, in either its free cationic or bound form, potently arrested cell proliferation. This arrest was non-cytotoxic and was confined to the G1 phase of the cell cycle. Products of di-oxidized spermine autodegradation, including trace amounts of stable and cytotoxic acrolein (arrested S phase), were unlikely to have contributed significantly to the arrest.

Acrolein↗
PubMed1978

The identification of a cell culture inhibitor in a tumour extract.

An extract of Harding-Passey mouse melanoma was found to inhibit the proliferation of the same cell line grown in culture when measured by both thymidine incorporation and by the increase in cell number. The active ingredient was purified by ultrafiltration, column chromatography and preparative electrophoresis. The purified material was identified by mass spectrometry and by gas chromatography as spermidine. The partially purified material reversed the methylglyoxal Bis-guanyl hydrazone (Methyl-GAG) inhibition of cultured cells to the same extent as spermidine. Very low concentrations of Methyl-GAG were found to suppress the spermidine inhibition of thymidine incorporation into cells. The inhibitor extracted from melanoma tumours behaved in the same way as spermidine at all Methyl-GAG concentrations. Thus, it is unlikely that the active ingredient in the biological extract is anything other than spermidine.

Animals↗
PubMed1977

Hydroxyanisole-induced regression of the Harding-Passey melanoma in mice.

The drug p-hydroxyanisole (OHA) was found to inhibit the incorporation of 3H-thymidine in the Harding-Passey melanoma cells in culture. Because the cultured cells had lost some of their pigment-forming capacity, the enzyme tyrosinase was added to the culture. This greatly increased the sensitivity of the cells to OHA, strongly suggesting that cells producing the enzyme would be preferentially killed by the drug. An in-vivo study of the effect of OHA injected into tumour-bearing mice showed a beneficial effect, including increased survival time, reduction in tumour size and in many cases complete loss of tumour and no recurrence. An experiment with animals immunologically suppressed by radiation suggests that the effect is not an immunological one.

Animals↗