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Biomedical subjects

J Thacker

Publications and source records attributed to J Thacker.

At least 91 records · Page 5Linked to original sources
PubMed1977

Inactivation and mutation of cultured mammalian cells by aluminium characteristic ultrasoft X-rays. I. Properties of aluminium X-rays and preliminary experiments with Chinese hamster cells.

Irradiation with ultrasoft X-rays produces electron tracks of short defined lengths in the irradiated material. This property is of particular interest in distinguishing between different models of radiation action on living organisms. The production, absorption and dosimetry of aluminium K characteristic X-rays of energy 1.5 keV are described. Quantitative experiments on mammalian cells with these X-rays are possible, and they were found to be considerably more effective than gamma-rays in inactivating Chinese hamster V79 cells in vitro.

Cell Survival↗
PubMed1977

Inactivation and mutation of cultured mammalian cells by aluminium characteristic ultrasoft X-rays. II. Dose-responses of Chinese hamster and human diploid cells to aluminium X-rays and radiations of different LET.

The induction of inactivation and mutation to thioguanine-resistance of two types of cultured mammalian cells, V79 Chinese hamster and HF19 human diploid, was studied after irradiation with aluminium K characteristic ultrasoft X-rays, helium ion track intersections of different LET, 42 MeV d-Be neutrons, and hard X- or gamma-rays. The form of the dose-response curves was different for the two cell-types, and there was an overall difference in radiosensitivity, the human cells being the more sensitive to all radiations. However, for both inactivation and mutation-induction, the relative responses of both cell-types to these radiations was similar. Aluminium X-rays were considerably more effective than hard X- or gamma-rays and were at least as effective as helium ions of 20-28 keV micron-1, although aluminium X-rays produce tracks of very limited range (less than about 0.07 micron). Single track effects by aluminium X-rays cannot, therefore, extend beyond about 0.07 micron, and the subcellular sites involved in inactivation and mutation cannot be greater than this dimension or else the effectiveness of aluminium X-rays would be similar to that of low-LET radiations. This observation is in contradiction to models of radiation action which require relatively large sensitive sites; for example the 'theory of dual radiation action' requires a site diameter of about 0.4 micron to explain the shape of the dose-response curves for V79 hamster cells.

Cell Survival↗
PubMed1976

Factors affecting the efficiency of purine analogues as selective agents for mutants of mammalian cells induced by ionising radiation.

In the Chinese hamster cell line V79-4, the frequencies of the cells selected for their resistance to purine analogues do not always reflect the true frequencies of resistant mutants. The frequency of cells resistant to 8-azaguanine varied widely, especially when different sources of serum were used in the selective medium. Even with the more efficient analogue, 6-thioguanine, small colonies arose in the selective medium at a frequency which was strongly dependent upon analogue concentration and viable cell seeding density. These colonies were shown to have a phenotype which was indistinguishable from wild type. Hence with irradiated cells, where the viability of the cell population is reduced to an extent varying with the dose and the interval allowed for mutant expression, the counting of all colonies arising in selective medium can lead to spuriously variable, and sometimes very high, "mutation frequencies". Although the frequency of wild type colonies selected in thioguanine was diminished by the use of high concentrations of the analogue, a loss of induced mutants also occurred at these concentrations. Further, the V79-4 line contained two distinct types of mutant with different levels of hypoxanthine-guanine phosphoribosyl transferase (HGPRT) activity, and only of these types (HGPRT-negative mutants) increased in frequency with radiation dose. These results can account for many of the anomalies encountered in previous studies with purine analogues as selective agents, and show that some care has to be taken to characterize the mutants selected by resistance to purine analogues before meaningful dose-response relationships can be established.

Aneuploidy↗
PubMed1976

The induction of mutation in yeast by hydrogen peroxide.

The inactivation and mutation to respiratory deficiency of yeast cells by H2O2 are shown to vary progressively with the phase of cell growth, with a sharp transition occurring as the cells complete logarithmic growth. Respiratory deficient mutants isolated from the wild-type population are of two types, one of which is much more sensitive to H2O2 but forms only a small fraction of the mutant sub-population. Based upon the response of the more resistant type, mutation frequency increases appear to result from selection of pre-existing mutants in log phase populations, while induction occurs in stationary phase cells. The induced mutation frequency fits a (dose)2 relationship, but the frequency is depressed when the dose is high (or number of cells treated is low). All the induced mutants are extranuclear and of the resistant type, and show a wide range of suppressiveness in crosses to respiratory competent cells. This may indicate mitochondrial DNA is altered to different extents by H2O2; by the same criterion, the spontaneously occurring H2O2 -sensitive mutants retain a large amount of mitochondrial DNA information, in agreement with their colonial morphology. A small increase in forward mutation of nuclear genes was also found after H2O2 treatment. Parallels are drawn between the response of yeast cells to ionising radiation and to H2O2, and it is suggested that radical action may be involved in inactivation and mitochondrial genome mutation induced by both agents.

DNA↗
PubMed1976

The crush injury: a high risk wound.

A standardized experimental impact injury model was developed to produce soft tissue trauma that simulated impact injuries to soft tissue overlying the cranium. An aluminum impact instrument was constructed so as to deliver a measured amount of energy to a finite area of soft tissue over a fixed foundation. Impact injury resulted in readily demonstrable changes in the morphology of the tissue and its blood flow. As measured by the distribution of fluorescein dye, the blood flow to the impact site was considerably less than that to unwounded tissue. The magnitude of this reduction in blood flow to the site of injury was proportional to the level of energy absorbed by the tissue. The injury to skin resulting from the impact was restricted primarily to the subcutaneous tissue and panniculus carnosus. Loss of adipose tissue and necrosis of skeletal muscle fibers in these layers were associated with the development of a dense inflammatory infiltrate. The structural damage to the tissue and its reduced perfusion were correlated with the tissue's increased susceptibility to infection by bacteria delivered either by direct infection or as a result of a bacteremia. The magnitude of this damage to the host's defenses is, again, directly related to the amount of energy absorbed per unit area of soft tissue. Antibiotics did suppress the growth of bacteria in these experimental soft tissue impact wounds, even when treatment was delayed eight hours. While the therapeutic efficacy of antibiotics was readily apparent in soft tissue impact wounds, the degree to which they could suppress bacteria in these wounds was less than that encountered in the treated control wounds not subjected to impact.

Adipose Tissue↗
PubMed1976

The use of Drosophila to estimate the possibility of genetic hazard from ultrasound irradiations.

Flies of the species Drosophila melanogaster have been irradiated with 1 MHz ultrasound at intensities of 0-05-2 W cm-2. The flies were immersed in water and rotated in the ultrasound field to ensure that they were adequately exposed to the radiation. Immersion and rotation alone were not found to impair subsequent survival and fertility of the flies. At the higher intensities of irradiation, the flies were found to be killed in direct proportion to the duration of the irradiation. However, large-scale breeding experiments with flies surviving irradiation showed that no significant increase in the frequency of recessive lethal mutation (Muller 5 system) and chromosomal non-disjunction (Clark-Sobels system) had occurred. Taken with other recent studies, this result suggests there is little risk of genetic damage to multicellular organisms from ultrasound irradiations at frequencies and intensities currently used in medical practice.

Animals↗
PubMed1975

Inactivation and mutation of yeast cells by hydrogen peroxide.

It has been found that inactivation and mutation to respiratory deficiency of yeast cells can be induced by hydrogen peroxide treatment. However, considerable inconsistencies were encountered in measuring these responses. The inconsistencies were found to arise from differences in the abilities of cells in different metabolic states to destroy H2O2 and in the intrinsic sensitivities of cells in different growth states. Parallels are drawn with previous inactivation data from bacterial studies suggesting reparable lesions in DNA provide a useful model to explain H2O2-induced inactivation, but it is not yet possible to eliminate alternative interpretations. Mutation induction in stationary phase cells is strongly depressed at high "doses" of H2O2 (or low cell survival), as is found with a variety of other agents.

Adenine↗
PubMedDate not supplied

Inherited sensitivity to X-rays in man.

Ataxia-telangiectasia (A-T), an inherited disorder giving radiation sensitivity and cancer-proneness, is discussed in terms of a defect in ability to repair DNA damage. A new assay using damaged recombinant DNA molecules suggests that the fidelity of repair of DNA double-strand breaks is reduced in an A-T cell line. Specific chromosomal changes in some A-T patients appear to be associated with cancer induction, and it is suggested that these could be linked to a DNA repair-fidelity defect. However, a general correlation between radiosensitivity and cancer-proneness is difficult to establish at present, partly because of diversity in radiosensitivity in the normal population.

Ataxia Telangiectasia↗