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Biomedical subjects

G Deknudt

Publications and source records attributed to G Deknudt.

At least 19 recordsLinked to original sources

Sampling times in micronucleus testing.

A series of micronucleus inducers were evaluated in the mouse bone marrow micronucleus test to determine if a 72-h sampling time enhances the sensitivity for detecting genotoxic agents. Male and female Swiss albino mice were dosed once with 7,12- dimethylbenz[a]anthracene, 6-mercaptopurine, benzo[a]pyrene, benzene, cyclophosphamide, 2-acetylaminofluorene, tubulazole, or mitomycin C. According to the EEC and OECD guidelines, the mice were killed at 24, 48 and 72 h after dosing. All test compounds induced an increase in the number of micronucleated polychromatic erythrocytes at 24 and/or 48 h. From the results obtained, it was evident that the 72-h sampling time does not enhance the sensitivity of the micronucleus test. The present data show that for screening purposes two sampling times at 24 and 48 h are sufficient to detect clastogens as well as aneugens. Although quantitative differences were found in sensitivity to micronucleus inducers between male and female mice, no qualitative differences were observed between the two sexes.

Animals↗

[In vitro study of the influence of donor age, nature of mitogen and exposure to X-rays on the proliferation rate of human lymphocytes].

Proliferation of lymphocytes from donors belonging to 4 age groups (2, 25, 45 and 80 years) and exposed, in vitro, to 0 or 2 Gy of X-rays was studied in cultures stimulated by 3 different mitogens. Our results show that these 3 factors (age, irradiation and mitogen) play a role in the frequencies of cells observed in first, second, third or subsequent cell division in 48 or 72 h cultures.

Adult↗

Frequencies of chromosomal aberrations induced in human blood lymphocytes by low doses of X-rays.

The dose-response for radiation-induced chromosome aberrations in human lymphocytes is usually fitted to the quadratic model. This assumes that the slope is essentially linear at low doses. Empirical observations of linearity at less than 200 mGy are, however, sparse. Some data have been published indicating a non-linear (threshold) response and these are reviewed. In particular one study with X-rays showed a plateau in response up to 50 mGy and with a significant dip below the control level at 4 mGy. The mechanism proposed to explain non-linearity is that low doses stimulate the enzymic repair capability of lymphocytes. Preliminary data are presented from a large experiment by six laboratories in which the low dose-response for X-rays has been re-examined. The plateau in the dose-response relationship, if it exists, does not extend to doses above approximately 10 mGy. No irradiated cells yielded aberration levels significantly below the control. Over the range 0-300 mGy the response can be fitted to a linear regression. There are, however, variations in sensitivity between cells from different donors. An unexpected finding was that some lymphocytes contained greater than 1 exchange aberrations. This may indicate a small subset of cells that are especially susceptible to the induction of aberrations by low doses.

Adult↗

Chromosome aberrations in mixed cultures of in vitro irradiated and unirradiated human lymphocytes.

Human whole blood samples were exposed to different doses (1, 2, 4, 6 or 10 Gy) of gamma-radiation and mixed with different volumes of non-irradiated blood before culturing to simulate partial body irradiations. Chromosome aberrations were analysed and the frequency of dicentrics was found to be lower than expected, particularly when irradiated blood was mixed with large volumes of non-irradiated blood and after exposure to high radiation doses. For the mixtures of irradiated and unirradiated blood the deviation from the Poisson distribution depends on the respective proportions and on the doses. The results can be correlated to in vivo aberration frequencies in case of therapeutical treatments, but the yields of aberrations are generally underestimated in vitro.

Chromosome Aberrations↗

Chemical induction of sister-chromatid exchanges in human lymphocytes treated in G0 prior to stimulation by different mitogens and revealed 72 h later in second division cells.

Frequencies of sister-chromatid exchanges (SCE) were determined in second-division metaphases of human lymphocytes, exposed for 1 h during the G0 phase to mitomycin C (MMC) alone or to cyclophosphamide (CP) in the presence of S9 mix. The cells were then cultured for 72 h in the presence of phytohemagglutinin (PHA), concanavalin A (Con A), Wistaria floribunda (WFA) or Lens culinaris (LcH-A) extracts. Large differences in mitotic indices (MI) and cell-cycle kinetics were observed among cells subjected to the various treatments. However, in the controls as well as in the cultures submitted to a G0 mutagenic exposure, the yield of SCE was not influenced by the mitogenic agent and was, therefore, independent of the proliferation properties of the cultured lymphocyte population.

Cell Cycle↗

In vivo studies in male mice on the mutagenic effects of inorganic arsenic.

The ability of sodium meta-arsenite (NaAsO2) to produce genetic damage in vivo has been evaluated in mice by the micronucleus test on bone marrow cells and the dominant lethality and sperm abnormality assays on male germ cells. The dose-related linear increase of micronuclei observed in somatic cells together with the negative results obtained in reproductive cells suggest that NaAsO2, under the conditions of the present experiments, displays clastogenic properties in vivo in laboratory animals, but is unable to produce heritable damage.

Animals↗

[Mutagen sensitivity and the repair process of the lymphocytes in the Werner syndrome].

In this study, we analyzed the cell cycle kinetics, the radiosensitivity, the repair process and the induction of sister chromatid exchanges in lymphocytes from the Werner's syndrome. When compared to a normal population, no statistical significant differences were observed for the cell cycle kinetics and the radiosensitivity. However, differences exist with respect to the repair process and lymphocytes from the Werner's syndrome are much more sensitive to the induction of SCE's.

Adult↗

[Effect of cytosine arabinoside on the cell cycle and level of radiation-induced chromosome anomalies in lymphocytes of mammals].

A treatment by cytosine arabinoside (ara-C), an inhibitor of repair, and by deoxycytidine, which reverse the inhibition activity of ara-C, has been used to study the duration of repair in X-irradiated mammalian lymphocytes. In human the repair requires at least three hours but is already completed within two hours for rabbit lymphocytes. The results appear rather surprising for pig lymphocytes because addition of ara-C to culture medium does not modify apparently the yield of aberrations.

Animals↗

Lack of mutagenic activity of white spirit.

The mutagenic potential of white spirit, a typical mixture of primarily aliphatic hydrocarbons used as a solvent, was investigated using a battery of test systems. The ability of this compound to induce gene mutations was assayed by the Ames' test with different strains of Salmonella typhimurium; its potential clastogenicity was tested in vivo on mouse bone marrow cells; in vitro induction of sister chromatid exchanges was studied in human lymphocytes. Negative results were obtained in all test systems. It is concluded that, in spite of its evident toxicity, white spirit does not display mutagenic properties.

Animals↗

Influence of various mitogens on the yield of sister-chromatid exchanges, induced by chemicals, in human lymphocytes.

The fluorochrome-plus-Giemsa (FPG) method of Perry and Wolff was used to compare the frequencies of sister-chromatid exchanges (SCEs) induced by cyclophosphamide (CP) or mitomycin C (MMC) in human lymphocytes stimulated by phytohaemagglutinin (PHA), concanavalin A (Con A), Wistaria floribunda (WFA), or lentil lectin (LcH-A) extracts. These 4 mitogens, differing in lectin valency and/or sugar specificity, are considered as activating primarily thymus-derived (T) lymphocytes. Regardless of the mitogen used, control cultures displayed a mean yield of about 8 SCEs/cell. A contact, of 1 h, with mitomycin alone or with cyclophosphamide and enzymatic activation, resulted in a significant augmentation of SCEs dependent on the mitogen used. An approximately 2-fold, 4-fold, or 6-fold increase in SCEs was observed for the cultures stimulated by PHA, Con A, and WFA or LcH-A respectively. Furthermore, there were mitogen-dependent differences in mitotic indices and cell-cycle kinetics in human lymphocytes harvested 72 h after stimulation.

Antibiotics, Antineoplastic↗

[Comparison in vivo of the clastogenic properties of busulfan and cyclophosphamide].

Cyclophosphamide was given i.p. to male and female mice in order to study the dose--and the time--response relationship for structural chromosome aberrations induced in bone marrow cells. The results were compared to previous observations made with busulfan. After injection of cyclophosphamide the frequency of abnormal cells is maximal after 24 hours and decreases rapidly at longer intervals At comparable doses, the percentage of damaged cells is higher after treatment with busulfan and, due probably to the low solubility of the compound, reaches a maximum only after 48 hours. These results confirm that the most obvious potential drawback of this short term test is the transient nature of such anomalies.

Animals↗

Mutagenicity tests with nickel salts in the male mouse.

The ability of NiCl2 and Ni(NO3)2 to induce chromosome aberrations in vivo in male mouse has been tested by the micronucleus test and the dominant lethality test. NiCl2 as well as Ni(NO3)2 failed to produce micronuclei in polychromatic erythrocytes whereas cyclophosphamide, used as positive control, raised their incidence markedly. In contrast to the results obtained with cyclophosphamide, NiCl2 and Ni(NO3)2 did not increase the rate of post-implantation death. These compounds decreased significantly, however, the rate of pregnancy as well as the amount of pre-implantation loss. Taking into account also the data in the literature, it is concluded that nickel probably has no clastogenic properties in mammals.

Animals↗

Cell kinetics and radiosensitivity of human lymphocytes stimulated by phytohemagglutinin, Wistaria floribunda or Lentil lectin.

The cell kinetics and the radiosensitivities of human lymphocytes (four donors) exposed to 200 rads of X-rays and stimulated with phytohemagglutinin (PHA), Wistaria floribunda (WFA) or Lens culinaris (LcH-A) extracts have been compared after cultivation times from 42 up to 54 h. All these mitogens are considered activating primarily T lymphocytes. PHA is a tetrameric molecule, whereas WFA as well as LcH-A are dimeric structures having only two reactive sites. PHA displays a higher mitogenic activity than WFA, while LcH-A is much less active than PHA and WFA. After 42 h of culturing, only metaphases of the first mitosis are found, irrespective of the mitogen used. With increasing cultivation times, however, differences in the cell kinetics have been observed for the different mitogens. Furthermore, no differences in radiosensitivity of lymphocytes stimulated by these mitogens were observed when cells are analyzed exclusively in their first mitosis.

Humans↗

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↗

[Clastogenic effects of zinc in mammals].

The eventual clastogenic properties of zinc chloride have been assessed as well in vitro as in vivo studies on mammalian somatic cells. For this purpose, human peripheral lymphocytes were treated in 48 or 72 hours cultures with 0, 20 or 200 micrograms zinc chloride, whereas C57Bl mice have received during one month a normal or poor calcium diet in combination or not with 0.5 g % of zinc. Chromosome analysis of treated human lymphocytes and of bone marrow cells of mice fed a poor dietary calcium supplemented with zinc has shown a significant increase in structural chromosome aberrations.

Animals↗

[Cell kinetics and radiosensitivity of Cercopithecus aethiops sabaceus lymphocytes stimulated by phytohemagglutinin].

The use of the BudR-Giemsa technique has shown that the peripheral blood lymphocytes of Cercopithecus aethiops sabaceus display a very fast answer to PHA-stimulation. At 32 h culture time numerous mitoses are already present and at 48 h more than 30% of the dividing cells are in second mitosis. Exposure to X-irradiation results in a higher incidence of unstable aberrations than in human lymphocytes.

Animals↗