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Biomedical subjects

E J Hall

Publications and source records attributed to E J Hall.

At least 271 records · Page 15Linked to original sources

Thermal tolerance and repair of thermal damage by cultured cells.

Exposure of hamster cells to 42.5 degrees C for long periods leads to the development of thermal tolerance; the slope of the survival curve become shallower after about 3.5 to 4 hours. If two 4-hour exposures at 42.5 degrees C are separated by various periods of time, thermal tolerance is eliminated by 20 hours. Prolonged exposure at 42.5 degrees C offers considerable protection from subsequent treatments to acute hyperthermia at 45 degrees C indicate or in conditioned medium or balanced salt solution failed to reveal any evidence of repair of potentially lethal damage.

Animals↗

Repair of potentially lethan radiation damage: comparison of neutron and X-ray RBE and implications for radiation therapy.

Experiments with Chinese hamster cells have shown that neutron irradiation does not result in repair of potentially lethal damage (PLD), i.e., that which can be influenced by changes in environmental conditions following irradiation. Since PLD is presumed to be repaired in tumors but not in normal tissues, this absence of differential sparing of tumor cells relative to normal tissues--a feature characteristic of irradiation with x rays--represents an advantage of neutrons in addition to their reduced oxygen effect. At a given dose, the difference in relative biological effectiveness (RBE) between tumors and normal tissues corresponds to a 5% increase in tumor dose with no concomitant increase in dose to normal tissues, which could be significant in cancer therapy.

Animals↗

Conditioned medium from plateau-phase cells. Effect on growth of proliferative cells and on repair of potentially lethal radiation damage.

In vitro cell cultures grown into plateau phase may be more suitable than exponentially growing cells as a model for tumor cell growth in vivo. Conditioned medium extracted from cells in plateau phase inhibits growth of log-phase cultures of either the same or a different cell line. Attempts to demonstrate that this inhibition is due to a heat-labile diffusible substance have failed. Conditioned medium extracted from plateau-phase cultures was effective in enhancing repair of potentially lethal damage following x irradiation. Cell survival is significantly increased following a six-hour postirradiation culture in conditioned medium as opposed to complete fresh medium.

Animals↗

Radiobiological properties of high-energy cyclotron-produced neutrons used for radiotherapy.

Radiobiological properties of high-energy cyclotron-produced neutrons were investigated. The survival curve for mammalian cells exposed to 35 MeV neutrons has an appreciable shoulder, but exhibits a significant initial slope at low doses. split-dose experiments, using doses comparable to the daily fractions of neutron therapy, indicate no repair of sublethal damage. The nitroimidazoles, and particularly Flagyl, have been shown to selectively sensitize hypoxic cells to the effects of x-rays. Experiments demonstrated that Flagyl is equally effective in reducing the oxygen enhancement ratio for high-energy neutrons. Hypoxic sensitizers must by regarded as an adjunct to neutron therapy, rather than as a competitor.

Animals↗

Hyperthermia: biological studies at the cellular level.

Tissue culture techniques were used to study the effect of hyperthermia on several cell types, including normal liver and hepatoma cells, as well as cell lines that have been established in culture for many years. Short exposures (less than 30 min.) at 45 degrees C readily kill a large proportion of cells. The response to heat was strikingly similar in all cells tested, and no preferential killing of neoplastic cells could be demonstrated. By contrast, hypoxic cells were found to be dramatically more susceptible to killing by heat than aerated cells. This is the reverse of the situation for x irradiation. The effectiveness of x irradiation was potentiated by treating the irradiated cells for 20 min. at 43 degrees C, which did not kill a detectable number of cells.

Cell Division↗

Hypoxic sensitizers: radiobiological studies at the cellular level.

The nitroimidazoles have been found to selectively sensitize hypoxic cells to the effects of irradiation. The latest in this family of drugs is RO-07-0582, which is able to mimic 80% of the oxygen effect at a concentration of 5 mM by modifying the sensitivity of hypoxic cells to single doses of gamma rays; however, it is not a substitution for oxygen in promoting the repair of sublethal radiation damage between split doses. Studies show that it is a powerful cytotoxic agent as well and selectively operates against hypoxic cells.

Animals↗

The potential of californium-252 in radiotherapy. Preclinical measurements in physics and radiobiology.

Californium-252 is a man-made radionuclide (half-life 2-65 years) which emits a mixture of neutrons and gamma rays. It is used in radiotherapy as an alternative to radium and extends the potential benefits of neutrons to interstitial and intracavitary applications. Gamma rays account for a variable proportion of the dose (30 to 50 per cent), depending on the source filtration and the distance from the source. Dosimetry is complicated by this mixture of neutrons and gamma rays. However, measurements with paired ion-chambers, together with Monte-Carlo calculations, have produced dosimetric data that are adequate for clinical use. Many determinations of the oxygen enhancement ratio (OER) have been reported. At the low dose-rates characteristic of interstitial implants, the OER is about 1-5. This is essentially the figure for fast neutrons alone, since at very low dose-rates the contribution of the gamma rays to the biological effect is negligible. As the dose increases, there is a corresponding rise in the OER because the gamma ray contribution can no longer be ignored. The OER is likely to be about 1-8 if 252Cf is used in intracavity treatments and 2-0 if used in "acute" exposures in devices such as the Cathetron. The relative biological effectivenesss (RBE) varies with dose-rate, and with the biological system used to measure it. Radiobiological experiments indicate that 6,000 rads of radium gamma rays in seven days is equivalent to 890 rads of 252Cf neutrons delivered in approximately the same overall time. This figure was suggested some years ago as an interim guide-line until sufficient clinical experience is accumulated.

Animals↗

A review of high LET facilities, existing and projected, with emphasis on the radiobiologic aspects.

The introduction of high LET radiations into radiotherapy is an exciting development. Neutron facilities are already in clinical use in England and the United States, while machines to produce negative pi mesons and high energy heavy ions are in an advanced stage of development in Canada, the United States and Europe. The state of the art at each of these installations is reviewed. The therapeutic merits of various heavy particles are compared with conventional photon beams. Lowering the OER (oxygen enhancement ratio) and improvement in the depth dose pattern are the principal advantages sought. Neutrons result in a somewhat lower OER but offer depth-dose patterns that are barely the equal of x- and gamma-rays. Protons by contrast produce excellent dose distributions, but no reduction of OER. Negative pi mesons improve both depth dose pattern and OER to some extent. High energy heavy nuclei show the greatest promise as far as lowering the OER is concerned, but will probably not equal pions in depth dose pattern. More radiobiologic data are urgently needed for all of these new radiation modalities.

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