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Biomedical subjects

E J Hall

Publications and source records attributed to E J Hall.

At least 253 records · Page 14Linked to original sources
PubMed1979

Misonidazole and MTDQ in combination: cytotoxic and radiosensitizing properties in hypoxic mammalian cells.

A combination of misonidazole and MTDQ (6,6'-methylene-bis-2,2,4 trimethyl-1,2-dihydroquinoline) has been tested for its radiation-sensitizing properties and cytotoxicity, using Chinese hamster V79 cells cultured in vitro. Both compounds sensitize hypoxic cells to the effects of X-rays, and when used in combination their sensitizing properties are additive. By contrast, the presence of MTDQ completely inhibits the cytotoxicity that misonidazole exhibits towards hypoxic cells. These experiments shed some light on the mechanism of action of electron-affinic hypoxic cell sensitizers, and the combination of radiosensitizers suggested may have an application in human cancer radiotherapy by eliminating the neurotoxicity experienced by patients receiving misonidazole during radiotherapy.

Animals↗
PubMed1979

Oncogenic transformation of mammalian cells in vitro with split doses of x-rays.

An established line of mouse fibroblasts, C3H/10T1/2 cells, was used for the assessment in vitro of oncogenic transformations caused by single and split doses of x-rays. The shape of the dose-response relationship was determined over the range from 0.1 to 10 Gy. It was found that splitting the x-ray dose into two equal fractions, separated by 5 hr, led to a reduction in transformation frequency at doses above 1.5-2 Gy but to an enhancement of transformation at lower doses. The observations reported cast doubt on the assessment of human cancer risk at lo dose levels by a linear extrapolation from available high-dose data from the Japanese atomic bomb survivors or from persons exposed for medical purposes.

Animals↗
PubMed1979

Pressure sores-a reappraisal.

Pressure sores are a common problem. They are casually accepted, their etiology is well defined, and treatment is standardized. How, therefore, can the subject justify reappraisal? On detailed review, evidence is presented showing that pressure sores can be minimized, that their pathophysiology is far from certain, and that their management is changing dramatically. During the past decade, new preventive measures have been adopted consisting of multidisciplinary tissue trauma clinics for paraplegic patients, based in rehabilitation hospitals, as well as early identification of the "at-risk" subgroup of geriatric patients who will require aggressive nursing care. Although pressure is the most widely accepted etiological factor, no sophisticated experimental studies have corroborated this hypothesis, and in fact, the majority of research conflicts with clinical observations. Recently, new surgical proceudres-myocutaneous and sensory skin flaps-have been devised to solve complex coverage problems which will possibly reduce the recurrence rate. An in-depth review of pressure sores is therefore warranted and will, we hope, stimulate renewed interest in this all-too-frequent clinical affliction.

Aging↗
PubMed1978

Oncogenic transformation in vitro by the hypoxic cell sensitizer misonidazole.

The hypoxic cell sensitizer Misonidazole (Ro-07-0582) induces oncogenic transformations in the C3H/10T1/2 mouse embryo cell line cultured in vitro. A drug concentration of 0.4 mM applied to aerated cells for 3 or 6 days results in a transformation rate comparable to that observed following an X-ray dose of 1 Gray. A higher drug concentration of 6.0 mM is equivalent to 4 Gy. The combination of Misonidazole and X-rays produces a significant increase in the frequency of transformation over either drug or radiation alone, but the data are equivocal on the question of additivity vs synergism.

Cell Line↗
PubMed1978

Studies with bleomycin and misonidazole on aerated and hypoxic cells.

Bleomycin is a chemotherapuetic drug used primarily in the treatment of squamous-cell carcinoma, while misonidazole is an effective radiosensitizer and potent cytotoxic agent selectively affecting hypoxic cells. V79 Chinese hamster cells were used to investigate the cytotoxicity of bleomycin (BLM) under aerated and hypoxic conditions as a function of drug concentration. At a lowered temperature of 17.5 degrees C, or at an elevated temperature of 42.5 degrees C, hypoxic cells are more sensitive to killing by BLM than aerated cells. At either of these temperatures, progression through the cell cycle is inhibited. However, at 37.5 degrees C, mimicking a clinical situation, the sensitivies are reversed, and hypoxic cells are appreciably more resistant. Although many factors are involved, the major reason for this is that aerated cells are cycling while hypoxic cells are not. Aerated cells can progress into phases of the cell cycle where they are more sensitive to killing by BLM. Misoinidazole (=Ro-07-0582) was used in combination with BLM, since its mode of action has been shown to be psecific for killing hypoxic cells. It concomitant use with BLM could be of potential use in chemotherapy when confronted with the hypoxic cell component of solid tumours.

Bleomycin↗
PubMed1978

Hyperthermia and low dose-rate irradiation.

Hyperthermia combined with 60Co gamma irradiation was studied using V79 hamster cells cultured in vitro. Modest hyperthermia (41 degrees C for 6 hrs.) enhanced the cell killing produced by acute exposure to radiation. The same treatment enhanced the effect of low dose-rate irradiation (200 rads/hr.) even more. The sequence in which modest hyperthermia was combined with low dose-rate irradiation was important. Maximal enhancement was observed when hyperthermia was followed by irradiations. The probable explanation is that, by damaging the repair system, prior heat renders the cells unable to repair sublethal damage during subsequent low dose-rate irradiation.

Animals↗
PubMed1978

The nitroimidazoles as radiosensitizers and cytotoxic agents.

Using hamster cells in culture, the radiosensitizing and cytotoxic properties of 8 electron-affinic drugs have been compared. These include nitrofurans derivatives as well as 2 and 5-nitroimidazoles. Most work has been performed with misonidazole for which it appears that, at 37 degree C, the concentration of drug required to produce a given level of cell killing is inversely proportional to the square of the exposure time. Misonidazole was also compared with X-rays for its ability to produce neoplastic transformations in vitro, using the C3H 10T 1/2 cell line.

Cell Survival↗
PubMed1978

Cytological effects of 1-(2-nitro-1-imidazolyl)-3-methoxy-2-propanol (misonidazole) on hypoxic mammalian cells in vitro.

Hypoxic Chinese hamster V-79 cells were examined for light-microscope morphology, progression through the cell cycle, chromosomal aberrations, and viability, after incubation with the 2-nitroimidazole, misonidazole [1-(2-nitro-1-imidazolyl)-3 methoxy-2-propanol]. Cytological examination of cells up to 42 hr after incubation with the drug at 37 degrees indicated that increasing contact time and increasing drug concentrations interfered with cell attachment and progressively slowed cell progression through the cell cycle. Forty-two hr after a 5.5-hr treatment with 5 mM misonidazole, the majority of cells contained heteropyknotic nuclei, whereas less than 3% had progressed into mitosis. Of the few cells that reached mitosis by 42 hr, the level of chromosomal aberrations was 6 times that due to hypoxia alone. However, the majority of metaphases (70%) were unaltered; thus about 2% of the treated cell population passed into mitosis unaltered. After a 5.5-hr incubation with 5 mM misonidazole, 98% of the cells also had lost their ability to produce clones. It is suggested that the cytotoxic effect of this drug on hypoxic cells is that the cytotoxic effect of this drug on hypoxic cells is largely mediated via an interphase cell death, with a minor effect due to chromosome aberrations and cell death from genetic inequality of progeny cells. The ability of misonidazole to kill hypoxic, noncycline cells, which may limit the curability of some tumors with conventional X-rays or chemotherapy agents, makes it of considerable potential interest.

Anaerobiosis↗
PubMed1977

Cytotoxicity of Ro-07-0582; enhancement by hyperthermia and protection by cysteamine.

The selective cytotoxicity which Ro-07-0582 exhibits towards hypoxic cells is strongly temperature-dependent. This cytotoxicity is reduced by the radical scavenger cysteamine, suggesting that nitro radicals or nitroso intermediates are involved in cell killing by the drug. Chromosome aberrations are not induced by Ro-07-0582 even when the surviving fraction is reduced to 0-01.

Cell Survival↗