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Biomedical subjects

L Fabry

Publications and source records attributed to L Fabry.

At least 37 records · Page 2Linked to original sources

[The repair of DNA damage induced in human lymphocytes by gamma rays and fast neurons].

When Go human lymphocytes are exposed either to gamma-rays or to d(50)-Be neutrons and then immediately incubated in presence of cytosine arabinoside, the frequency of chromosomal aberrations which is normally observed after radiation exposure only is sharply increased. This enhancement of the aberrations, particularly the dicentrics, is, however, less marked when cytosine arabinoside is administered at longer intervals of time after irradiation. For gamma-rays, the treatment with cytosine arabinoside has no effect on the dicentrics yield when given 5 h after irradiation, indicating that the repair is completed within the 5 h after irradiation and that the lesions are not anymore available to produce exchange aberrations. For d(50)-Be neutrons, the time of repair takes approximately 5 h after a dose of 2.0 Gy, whereas it appears to be shorter (3 h) after a dose of 0.5 Gy.

Adult↗

[Relative biological effectiveness of weak doses of neutrons for the production of dicentric chromosomes in human lymphocytes].

The induction of dicentric chromosomes in G0 human lymphocytes has been used to determine the Relative Biological Effectiveness (RBE) of low doses of d(16 MeV)-Be, d(33 MeV)-Be and d(50 MeV)-Be neutrons. Comparison of the dose-response curves obtained for neutrons with that found for gamma-rays indicates that RBE increases with decreasing neutron dose and with decreasing neutron energy, from d(50 Mev)-Be to d(16 MeV)-Be neutrons. The maximum RBE value at low doses has been evaluated by the linear components of the dose-response curves. It is equal to 14.0, 6.2 and 4.7 for the d(16 MeV)-Be, d(33 MeV)-Be and d(50 MeV)-Be neutrons respectively, when compared with the effects produced by the gamma-rays from 60-Co.

Adult↗

In vitro and in vivo studies on the potential mutagenicity of alclofenac, dihydroxyalclofenac and alclofenac epoxide.

Alclofenac (A) and two of its metabolites, dihydroxyalclofenac (DHA) and alclofenac epoxide (AE), were tested for their mutagenic potential. Alclofenac and DHA showed no mutagenic, transforming or clastogenic potential in any in vitro experiment. The addition of a supplementary metabolic activation system did not change the response of those two compounds in any test procedures in vitro. AE, an intermediary metabolite between A and DHA, was mutagenic by itself in the Ames test, but in the presence of a liver post-mitochondrial fraction its activity of Salmonella typhimurium was greatly decreased. Dominant lethal mutations were not induced in male rats given alclofenac, and AE had no effect in the micronucleus test. In human volunteers given alclofenac at therapeutic dose levels, no mutagenic activity was found in the urine and no significant increase in the incidence of structural chromosome aberrations was observed in peripheral blood lymphocytes.

Animals↗

Lymphocyte chromosome aberrations in patients undergoing radiation therapy for mammary carcinoma.

Patients undergoing radiation therapy for mammary carcinoma have been cytologically examined for the presence of polycentric chromosomes in their peripheral blood lymphocytes. The mean values of the observed yields can be fitted to a quadratic function. Due probably to a lower number of lymphocytes exposed the curve now obtained gives a smaller aberration yield than the dose effect curves published earlier for patients given telecobalt therapy.

Adult↗

Mutagenicity tests with astemizole in vitro and in vivo.

Possible induction of chromosomal aberrations and/or sister chromatid exchanges by astemizole was studied in vitro on human lymphocytes. In vivo chromosomal damage was assessed by a micronucleus test on rats and a dominant lethal test on both male and female mice. All these tests yielded negative results for astemizole so that is can be concluded that astemizole has no potential to induce chromosomal aberrations.

Animals↗

The lymphocytes of small mammals. A model for research in cytogenetics?

The influence of nuclear characteristics such as chromosome number, chromosome arm number or amount of R-band material on the yield of radiation-induced chromosome aberrations has been re-evaluated on the basis of some recent experiments with the harlequin-staining method to distinguish the first from subsequent divisions. The results obtained up to now show that differences in cell kinetics of stimulated peripheral blood lymphocytes, causing a different distribution of first and following mitoses at the time of observation, can result in an underestimate of the incidence of unstable chromosome aberrations such as dicentric chromosomes when the observations are performed at a standardized fixation time without taking into account the cell generation. If, however, only first-division mitoses are considered, the radiosensitivity of the cells appears to be independent on nuclear characteristics. Furthermore, observations on whole-body irradiated animals show that, owing to the very short survival time of lymphocytes carrying chromosome aberrations, mammals generally available for such experiments represent inappropriate models when cytogenetic effects in somatic cells are to be followed for long periods of time after an acute exposure to ionizing radiation or after a chronic exposure.

Animals↗

Evaluation of radiation-induced chromosomal aberrations in human peripheral blood lymphocytes in vitro: result of an IAEA-coordinated programme.

The results of an IAEA coordinated programme on radiation induced chromosomal aberrations in human peripheral blood lymphocytes in vitro are presented. In a master experiment, a whole blood sample from one donor was irradiated with 200 R of X-rays. Different fixation times from 46 to 82 h were used. The progression of cells into mitosis was monitored by BrdUrd incorporation. 14 investigators took part in the scoring of chromosomal aberrations. The main conclusions of this study are: (1) The mean frequencies of aberrations changed with fixation time. (2) The number of cells scored as aberrant by different laboratories was very similar, but there was variability in the number of aberrations scored per aberrant cell. (3) The differences in the frequencies of aberrations between laboratories were minimal when the scoring was restricted to the first major peak of mitotic activity and sufficient cells were scored. It is concluded that using controlled experimentals conditions, human peripheral blood lymphocytes can effectively be used as a reliable biological dosimeter for absorbed radiation dose.

Argentina↗

Chromosome aberrations as a measure of mutagenesis: cytogenetic extrapolation from animal to man.

A reevaluation of the factors considered to affect the chromosomal sensitivity of mammalian peripheral blood lymphocytes has been made on the basis of some recent experiments using the harlequin-staining method to distinguish the first from subsequent divisions. Observations on human lymphocytes show that the mixing up of first and second or third cell cycle cells cannot explain all the variability between the experiments performed without bromodeoxyuridine labeling. Establishing a uniform methodology is also not likely to eliminate all causes of variation. Similar heterogeneity is observed for other mammalian species. Provided comparisons are restricted to results obtained within the same laboratory, some estimation of the relative sensitivity of chromosomes from different species is, however, possible.

Animals↗

[Response of human and rabbit lymphocytes to low doses of X-rays].

The response of human and rabbit lymphocytes to low doses of X-rays was studied by the yields of dicentrics in first division metaphases. For both species, the dose-response curve was best fitted to the linear-quadratic model with a linear component predominating up to 67 and 42 rad respectively for man and rabbit. A calibration curve (5-400 rad) was obtained by combining the present results on man with previous data at higher doses. On the other hand, it appears that, at low doses, the radiosensitivity of human lymphocytes is significantly higher than that of rabbit lymphocytes.

Animals↗

[Cell kinetics and radiosensitivity of cultured cow lymphocytes].

The harlequin-staining technique has been used to study, after PHA-stimulation, the cell proliferation of cow lymphocytes in culture and to assess the radiosensitivity in first mitosis cells. At the 48 h fixation time, only 34% of the cells are in first mitosis whereas 55% are already in second and 11% in third mitosis. The exposure of cow lymphocytes to 200 rad X-rays result in the production of 16% dicentric chromosomes in first mitosis cells.

Animals↗

Mutagenicity of n-nitrosodiethanolamine and its acetyl derivatives.

The mutagenicity of N-nitrosodiethanolamine and its mono- and di-acetyl derivatives was tested in the S. typhimurium test system, in cytogenetic studies and in the micronucleus test. N-nitrosodiethanolamine had no mutagenic effects towards several strains of S. typhimurium either in the absence or in the presence of metabolic activating systems. Its diacetyl derivative exerted mutagenic effects towards the S. typhimurium strains TA1530 and TA100. Neither compound increased significantly the nubmer of chromosomal aberrations or of micronuclei in mice.

Animals↗

Mutagenicity of aflatoxin B1: observations in vivo and their relation to in vitro activation.

Aflatoxin B1 (AFB1) was shown to be clastogenic in vivo on the basis of its capacity to produce micronucleated cells and chromosomal aberrations in mouse bone marrow cells. On the other hand, in vitro studies on cultured human lymphocytes suggested only a slight mutagenic action of AFB1. If, however, a microsomal extract isolated from rat liver was added together with the AFB1 (1.92 X 10(-5) M) to the lymphocytes before the incubation period, the yield of chromosomal aberrations and of sister chromatid exchanges (SCE) increased markedly indicating that AFB1 must be metabolically converted before it can act as an active mutagen. The use of microsomal extracts for in vitro tests can thus considerably improve the reliability of such tests of mutagenicity although studies in vitro will not be able to entirely replace those in vitro.

Aflatoxin B1↗

[Relationship between the induction of micronuclei in marrow cells by chromium salts and their carcinogenic properties].

The micronucleus test has been used to study the mutagenic activity of chromium derivatives and to examine the relationship between their carcinogenic properties and their ability to induce chromosomal damage. It has been found that potassium dichromate is a potent mutagen increasing, for instance, the rate of micro-nucleated erythrocytes while calcium chromate and chromic nitrate are ineffective. From our observations and the data on carcinogenicity, it can be concluded that the micronucleus test cannot be used to predict the carcinogenic properties of chromium derivatives.

Animals↗

Mutagenicity tests with griseofulvin.

Griseofulvin was studied for its ability to induce structural chromosomal aberrations in germ and somatic cells of the male mouse. It was also tested for its capacity to produce his+ revertants in Salmonella typhimurium. All tests yielded negative results, whereas highly significant effects were recorded in control assays with thio-TEPA.

Animals↗

[Kinetics of division of human and rabbit lymphocytes stimulated by phytohemagglutinin, studied by means of the bromodeoxyuridine (BUDR) technic].

The BUDR-Giemsa technique has been used to distinguish the first from later divisions for man and rabbit lymphocytes stimulated by treatment with phytohemagglutinin. At 48 hours, 99% of human lymphocytes exposed to 200 rads of X-rays are in first division whereas 45% of the rabbit lymphocytes are already in second division and 28% in third division.

Adult↗