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Biomedical subjects

E J Hall

Publications and source records attributed to E J Hall.

At least 217 records · Page 12Linked to original sources
PubMed1984

Magnetic resonance and ionizing radiation: a comparative evaluation in vitro of oncogenic and genotoxic potential.

This paper describes experiments designed to investigate possible biological hazards associated with magnetic resonance (MR) imaging. Mouse C3H 10T1/2 cells were exposed to a powerful magnetic field (up to 2.7 T) for periods up to 17 hours together with pulsed field gradients and radio-frequency excitation and compared with untreated controls and cells exposed to gamma rays (0.3 to 0.4 Gy). Several biological endpoints were studied. In the case of oncogenic transformation, no significant difference could be demonstrated between controls and either the gamma-irradiated or MR-exposed cells. When mitotic cells were examined for chromosomal alterations, the frequencies of both chromosomal aberrations per cell and sister chromatid exchanges per chromosome were significantly enhanced over control levels after ionizing radiation exposures but were similar to control (or less) after MR exposures. These studies confirm the known deleterious effects of ionizing radiation (even at low doses) for chromosomal damage, if not for oncogenic transformation, yet show that MR exposures even of long duration (up to 17 hours) at high field strengths (up to 2.7 T) do not result in effects greater than 0.3 Gy of gamma rays. Negative results do not conclusively rule out a health risk; however, the data clearly mitigate against an association between exposure to MR imaging modalities and both carcinogenic and genotoxic effects.

Animals↗
PubMed1984

Biological effects of heat.

The biological effects of heat appear to be favorable for its use to treat cancer. Heat kills cells in a predictable and repeatable way. The age response function complements X-rays in that S-phase cells are most sensitive, and at the same time cells that are at low pH or are nutritionally deprived are also more sensitive. This offers the possibility that cycling tumor cells and quiescent cells that have respired to hypoxia may be more sensitive to heat than are the slowly turning over cells of the normal tissues responsible for late effects. Thermotolerance, in general, represents a problem and a complication in clinical practice but may be exploited to advantage. The interaction of heat with ionizing radiation has been studied extensively and is complex; in general, heat inhibits the repair of both sublethal and potentially lethal X-ray damage, but it is not obvious how to exploit this to advantage. By contrast, the potentiation by heat of the action of chemotherapy agents has been relatively neglected. This is a promising area, since local hyperthermia can "target" drug action in a way not otherwise possible. Heat is a weak mutagen and has not been shown to be a carcinogen; this is a most desirable property at a time of increasing concern for the oncogenic potential of agents used to treat cancer.

Animals↗
PubMed1984

Oncogenic transformation systems involving mammalian cells in vitro to determine the relative risks of different treatment modalities.

Systems developed to assay oncogenic transformation in vitro represent a rapid and powerful tool to screen and compare carcinogens for their relative oncogenic potential as well as to search for compounds that reduce or inhibit carcinogenesis produced by both physical and chemical agents. An established line of mouse fibroblasts (10T1/2 cells) cultured in vitro were used to compare the incidence of oncogenic transformation produced by X-rays, heat, various hypoxic cell radiosensitizers and a range of commonly used chemotherapy agents. A variety of 2 and 5 substituted nitroimidazoles were tested; these included metronidazole, desmethylmisonidazole, misonidazole, SR-2508, SR-2555, Ro-0741, RSU-1047 and RSU-1021. Most of these sensitizers produced a similar level of transformation; for example a three day exposure of aerated cells to a concentration of 1 mM of the drug resulted in a transformation incidence comparable to 1 Gy of X-rays. The notable exception was SR-2508 which produced a five-fold higher incidence of transformation. The potential carcinogenicity of sensitizers must be considered in choosing which of the currently available new drugs is to be used in clinical trials as an alternative to misonidazole. A variety of chemotherapy agents were tested at a concentration comparable to those used clinically and matched to produce about the same amount of cell killing. It was found that the incidence of oncogenic transformation varied widely. Some agents, such as Vincristine did not produce transformation at a level that could be detected above background, while others such as cis-Platinum appear to be potent carcinogens and produced transformation at a rate an order of magnitude higher than can be achieved by any dose of X-rays. Hyperthermia in the range of 40 degrees C caused no transformation, whether or not the heat treatment was associated with significant cell killing. In addition modest hyperthermia appreciably reduced the transformation frequencies associated with X-ray doses. Superoxide dismutase (SOD), a known space free radical scavenger, has been shown to reduce the level of transformation produced by radiation and sensitizers. To be effective, SOD must be present for prolonged periods during the fixation and expression period of the transformation process.

Animals↗
PubMed1984

Encapsulated iodine-125 in radiation oncology. I. Study of the relative biological effectiveness (RBE) using low dose rate irradiation of mammalian cell cultures.

The use of encapsulated iodine-125 seeds has increased considerably since 1965, due largely to their physical characteristics. The 28 keV x-ray emission offers improved radiation protection and rapid fall-off of dose outside the treatment volume. The Relative Biological Effectiveness (RBE) of the low energy I-125 x-rays has not been adequately assessed. The limited studies have found a wide range of values, but most are between 1.2-1.5 relative to hard x-rays. We used C3H/10T1/2 mouse embryo cells in contact inhibited plateau phase to assess the RBE of I-125 seed x-rays relative to Cs-137 gamma rays (660 keV) using low dose rate continuous irradiation. Replicate experiments found the RBE to be 1.2. This did not vary with dose rate over the range of 10-76 cGy/hour. Calculations made from our cell survival data suggest that, in the case of permanent I-125 implants, where the dose is administered over a considerable period of time, the resultant surviving fraction of tumor cells is dictated largely by the length of the cell cycle. It is suggested that, for this reason, permanent I-125 implants may be less suitable for rapidly growing tumors, such as glioblastomas, than temporary I-125 implants, which are calculated to be virtually independent of the cell cycle duration.

Animals↗
PubMed1984

Encapsulated iodine-125 in radiation oncology. II. Study of the dose rate effect on potentially lethal damage repair (PLDR) using mammalian cell cultures in plateau phase.

Potentially lethal damage repair (PLDR) is considered to be an important mechanism of cellular radioresistance. Studies have suggested that radioresistant human tumor cells may have increased PLDR capability. Studies have also shown that PLDR may be decreased with smaller dose fractions. PLDR occurring with low dose rate continuous irradiation (LDCI) has not been assessed. The C3H/10T1/2 murine cell line in plateau phase (15% cycling fraction) was used to study the effect of dose fraction size and LDCI on PLDR. The cells were found to have substantial PLDR capability. Uncorrected data showed increased PLDR with higher single fractions. However, when the single fraction results are extrapolated to multiple fractions to give equivalent cell survival for the large and small fractions, no difference in PLDR was observed. The data from the LDCI experiments demonstrated some survival enhancement with delayed plating after 5 and 8 hours of irradiation, but not after 16 or more hours. The results indicate that PLDR occurs during the LDCI and that the magnitude of PLDR is similar for LDCI relative to acute irradiation.

Animals↗
PubMed1983

X rays may be twice as potent as gamma rays for malignant transformation at low doses.

The introduction in the 1950s of 60Co teletherapy units and megavoltage X-ray accelerators for radiotherapy prompted several studies which showed that the relative biological effectiveness (RBE) of orthovoltage X rays, compared with 60Co gamma rays, was approximately 1.1-1.2 (refs 1, 2). Subsequently, radiation therapists confirmed that the effect of established treatment protocols using orthovoltage X rays could be duplicated with the higher energy radiation by increasing the dose by approximately 10%, when radiation doses are of the order of tens of grays (or thousands of rads). The dependence of biological effectiveness on photon energy led to recommendations in which the quality factor, Q, which is an RBE for radiation protection purposes, was set at unity for X and gamma rays as well as for electrons or other directly ionizing particles having a linear energy transfer (LET) of less than 3.5 ke V microns-1. Over the past decade, however, several studies have shown differences in RBE between various low-LET radiations having LET values within the range designated for standard radiation. Underbrink et al. found an RBE for orthovoltage X rays relative to 60Co gamma rays of approximately 2 at 0.04 Gy, for induction of pink mutations in the stamen hairs of Tradescantia. Schmidt et al. scored chromosome aberrations in human lymphocytes, and at 0.25 Gy found the RBE of 200-k Vp X rays relative to 3-MeV electrons to be also approximately 2. Here we have compared 60Co gamma rays and orthovoltage X rays over the dose range 0.03-1.5 Gy using malignant transformation in mammalian cells in vitro as an end point. Our findings indicate that whereas the transformation incidence seems similar for X and gamma rays at high doses, the malignant potential of X rays is about twice that of gamma rays at 0.03 Gy.

Animals↗
PubMed1983

The contribution of the physical sciences to the development of radiation therapy.

Radiation therapy is used in the treatment of about half of all cancer patients in the United States. The development of this specialty has been intimately involved with major advances in the physical sciences, from the discovery of x-rays by Roentgen and radium by the Curies, to the technological breakthroughs of World War II that led to the 60cobalt teletherapy unit and the modern linear accelerator--the principal treatment machines in use today. These historical events are described and the principal characters introduced.

Elementary Particles↗
PubMed1983

The repair of sublethal damage in diploid human fibroblasts: a comparison between human and rodent cell lines.

Two diploid cell lines of human origin were irradiated in vitro. Repair of sublethal damage was observed in both lines when they were exposed to a single gamma-ray dose and incubated at 37 degrees C prior to receiving a graded second dose. In addition cells were irradiated at a low dose rate (56 or 76 rad/hr) and survival was compared to that after an acute exposure. A dose-rate effect was demonstrated. Sublethal damage repair was also studied using CHO or V-79 Chinese hamster cells, and the data suggest that the degree of repair is similar in human and rodent cell lines at photon doses up to 500 rad. The repair of sublethal damage can be a significant factor in the survival of human cells in vitro for fractionated doses.

Animals↗
PubMed1983

The sequential irradiation of mammalian cells with X rays and charged particles of high LET.

Chinese hamster V79 cells, synchronized in late-S phase, were irradiated with high-LET charged particles or X rays, or exposed sequentially to a single dose of charged particles followed by graded doses of X rays. The charged-particle irradiations consisted of deuterons (LET, 50 keV/microns) or 3He ions (96 or 160 keV/microns). The survival data obtained following the sequential irradiations show a synergistic effect compared with exposure to the low-LET radiation. An enhancement ratio is defined in order to quantify this effect. On the basis of this concept the present data show an enhanced interaction effect as the LET of the primary dose is increased or the size of this dose is increased. The data are also discussed in terms of a recent theoretical formulation which predicts synergism as a result of the interaction between the sublethal damage produced by the two radiations.

Animals↗
PubMed1982

Newly synthesized hypoxia-mediated drugs as radiosensitizers and cytotoxic agents.

Chinese hamster cells in culture were used to compare the radiosensitizing efficiency and cytotoxicity of misonidazole with several 2, 4 and 5 substituted nitroimidazoles. The two substituted compounds (SR 2508 and SR 2555) are similar to misonidazole in radiosensitizing effectiveness, but are significantly less toxic to hypoxic cells. This reduced cytotoxicity may result from either slower drug penetration or slower removal of non-protein sulfhydryl compounds (NPSH). The compound MJL-1-191-VII (a 4-nitroimidazole) is a much more effective radiosensitizer than would be predicted from its electron affinity. It appears to sensitize by two mechanisms, the first resulting from its electron affinity and the second as consequence of its rapid removal of endogeneous cellular NPSH; which are naturally occurring radioprotective substances.

Animals↗
PubMed1982

The particles compared.

Figure 5 represents an updated attempt to represent the dose distribution and high LET advantages of the various heavy particles, summarizing the conclusions discussed above. Neutrons are the cheapest form of high LET radiation. Their biological properties are excelled only by argon ions, but of course, they yield quite ordinary dose distributions. Protons give the best physical dose distribution and are by far the cheapest charged particles. Their biological properties, however, are similar to gamma-rays. Pions are comparable to carbon and neon ions in dose effect distribution, but are not as good because of dose/rate limitations and a less sharp edge to the beam. Two principal questions remain: 1. Are super dose distributions worth the substantial cost? 2. Do hypoxic cells limit radiocurability? These questions can only be answered in clinical trials and cannot even be addressed in the radiobiology laboratory.

Argon↗
PubMed1982

Studies with encapsulated 125I sources. I. Apparatus and dosimetry for determination of relative biological effectiveness.

Apparatus and dosimetry techniques have been developed which make possible studies of the biological effects of radiation from encapsulated 125I sources at clinically relevant dose rates using mammalian cells attached to culture dishes. The variation of dose rate from 125I photons as a function of distance from the interface between different materials was investigated. A polystyrene substrate changes the mean dose rate in attached cells by about 21%, depending on cell thickness. To reduce dosimetry uncertainty caused by this effect, special petri dishes were made from polyvinylidene fluoride, which changes the mean dose in attached cells by only 10%. Chinese hamster ovary cells attached to these dishes were cultured in incubators which contained 125I and 137Cs sources, allowing the effects of various dose rates (.005 to 0.80 Gy/hr) of radiation from the two isotopes to be compared. The relative dose rates from these low- and high-energy photons were measured with an accuracy of +/- 7% or better using an air-equivalent ionization chamber designed to resemble one of our special petri dishes. Calculations of dose rates from 125I give values within 4% of the measured dose rates used to determine the relative biological effectiveness of 125I photons.

Animals↗
PubMed1982

Studies with encapsulated 125I sources. II. Determination of the relative biological effectiveness using cultured mammalian cells.

Chinese hamster ovary (CHO) cells, in either exponential growth or unfed plateau phase were exposed to graded doses of radiation from Iodine-125 or from Cesium-137 at various dose-rates and the cells were assayed for reproductive integrity. From the patterns of cell survival obtained, the relative biological effectiveness (RBE) of the emission from 125I was determined relative to 137Cs. The RBE determined using cells in exponential growth was found to have a value of about 1.2, which was independent of the level of cell survival and did not vary over the dose-rate range from 7.5 to 53 cGy/hr. Using plateau phase cells the RBE has a constant value of about 1.3 between 13 to 46 cGy/hr, but is closer to 2.0 at lower dose-rates of 5 to 7 cGy/hr.

Animals↗