Biomedical subjects

R Stickler

Publications and source records attributed to R Stickler.

6 recordsLinked to original sources

PubMed1987

The effect of hypoxic cell sensitizers at different irradiation dose rates.

The effect of 0.1-5 mM misonidazole and SR 2508 on hypoxic V79 cellular survival at acute (498 cGy/min) and low (890 and 933 cGy/h) irradiation dose rates was measured and compared. The experiments were designed to delineate the oxygen mimetic phenomenon and the preincubation effect of these chemicals at these dose rates. Linear regression analysis of the survival data in terms of the linear quadratic model yielded values of alpha and beta. In the absence of drug, the linear coefficient was independent of dose rate, whereas the quadratic term was greatly reduced at low dose rate. At all dose rates, the preincubation effect affected primarily the alpha term, with little influence on beta. In contrast, the oxygen mimetic phenomenon predominantly affected the beta term. Overall, the radiosensitizing ability of these drugs was higher at low dose rate than at acute dose rate.

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PubMed1985

The variation of OER with dose rate.

The oxygen enhancement ratio (OER) has been measured as a function of dose rate from 276 Gy/hr to 0.89 Gy/hr for V-79 cells irradiated at 23 degrees C or 37 degrees C. As dose rate is decreased, the OER initially increases, from a value of 3.0, to a maximum value of 3.7 to 4.0, at a dose rate between 20 and 60 Gy/hr. The OER subsequently decreases with further dose rate reduction to a minimum value of 2.4 at the lowest dose rate. Similar experiments conducted with cells in nutrient deprived conditions exhibited a monotonic decrease in OER from 3.0 to 1.7 with dose rate reduction. These experimental findings can be understood in terms of the sublethal damage repair capability of cells under different pO2 and nutrient conditions.

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PubMed1985

Oxygen radiosensitisation at low dose rate.

Oxygen radiosensitisation has been studied at dose rates of 600, 3.37 and 0.89 Gy/h at pO2 levels of 0.001, 0.03, 0.1, 0.3, 1, 3, 10 and 21% in the gas phase. The oxygen enhancement ratio (OER), evaluated at 2% cellular survival, exhibited a decrease with dose rate from a value of 3.2 at the acute dose rate, to 2.4 at the lowest dose rate. This observation results from a decreased dose-rate effect on hypoxic cells, which is attributed to the partial suppression of sublethal damage (SLD) repair under hypoxic conditions. Oxygen radiosensitisation at the acute dose rate agrees with the calculated values based on the oxygen fixation hypothesis. Direct application of the Howard-Flanders and Moore equation to results obtained at low dose rate is not appropriate due to the influence of pO2 on SLD repair which affects radiosensitivity at low dose rate. When cells are irradiated at 3.37 Gy/h under nutrient-deprived condition (i.e. in Hanks balanced salt solution without glucose), low levels of oxygen appear to be more radioprotective than extreme hypoxia. Specifically, cells irradiated with 0.03% and 0.1% O2 are more radioresistant than cells under N2, with enhancement factors of 0.7 and 0.8, respectively. This phenomenon can be understood in terms of the ability of moderately hypoxic cells (0.03%-0.1% O2), and inability of anoxic cells, to repair SLD under nutrient deprived conditions. Radiosensitisation by these low levels of oxygen is insufficient to offset the difference caused by the disparate SLD repair capabilities.

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PubMed1985

Cellular and molecular repair of X-ray-induced damage: dependence on oxygen tension and nutritional status.

Cellular and molecular repair was studied at 23 degrees C using split-dose recovery and alkaline elution techniques, respectively, as a function of cellular oxygen and nutrient conditions. Hypoxic cells (0.001% O2) in full medium showed a partial reduction in the level of sublethal damage (SLD) repair relative to aerated cells (21% O2, OER equal to 3.2 relative to 0.001% O2); the respective repair kinetics were similar with a common repair half-time of 30 min. Similarly, hypoxic cells showed a slight reduction in strand break rejoining capacity compared to aerated cells. Under nutrient deprivation, anoxic cells displayed no SLD repair or strand break repair, while aerated cells exhibited the same level of SLD and strand break repair as for well-fed cells. In addition, nutrient deprived cells at low O2 levels (0.03%, OER equal to 1.15) displayed normal SLD and strand break repair capability. These results indicate that both nutrient and O2 deprivation are necessary for complete inhibition of cellular and molecular repair, and low levels of O2 (0.03%) can effectively reverse this inhibition.

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PubMed1984

Cell killing, radiosensitization and cell cycle redistribution induced by chronic hypoxia.

Some of the biological changes associated with extreme hypoxia at 37 degrees C (less than 10 ppm pO2) were examined in Chinese hamster V79 cells. Specifically, extreme hypoxia caused an initial decrease in plating efficiency to 55% in 4 hr after the onset of hypoxia. Beyond this time, the decline in plating efficiency was more gradual reaching 35% of control at 20 hr. Flow microfluorimetry (FMF) studies, in which cells are sorted on the basis of DNA content and then assayed for viability, demonstrated that mid S phase cells were most sensitive to chronic hypoxia, with surviving fraction equal to 2.5% at 20 hr. Furthermore, the viability of G1 and G2/M cells, after 20 hr of hypoxic storage, was also reduced to 20 and 7.6%, respectively. Hypoxia also caused alterations in the cell cycle distribution of initially asynchronous cells, as determined by dual parameter FMF measurements of both cellular DNA content and incorporated BudR. In particular, G2/M cells completed mitosis, while G1 cells showed little or no movement. Lastly, cells stored in chronic hypoxia displayed an enhanced radiosensitivity when compared to acutely hypoxic cells. Possible reasons for these observations are discussed.

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PubMed1984

Dose-rate effect between 1 and 10 Gy/min in mammalian cell culture.

A dose-rate effect is observed between 1 and 10 Gy/min for cultured Chinese hamster V-79 fibroblast cells irradiated under pO2 levels of less than 10 ppm, 100 ppm, 300 ppm and 21%. The dose for a cellular surviving fraction of 0.1% increases by 10-15% as the dose rate is changed from 10 to 1 Gy/min. This observed dose-rate effect is consistent with the repair of sublethal damage taking place during the radiation delivery. A related finding is that acute hypoxia in cell culture does not inhibit sublethal damage repair.

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