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1.
Toxicol Lett ; 115(3): 183-93, 2000 Jun 05.
Article in English | MEDLINE | ID: mdl-10814888

ABSTRACT

The effect of 10 microg/ml of adriamycin (doxorubicin) post-treatment was studied in HeLa cells exposed to 0, 0.5, 1, 2 and 3 Gy of gamma radiation. The survival of HeLa cells declined in a dose dependent manner in both irradiation+PBS and irradiation+ADR groups. Treatment of adriamycin immediately after irradiation resulted in a significant decline in the cell survival. The surviving fraction of HeLa cells reduced to 0.61 after exposure to 0. 5 Gy in the irradiation+ADR group, whereas a similar effect (i.e. surviving fraction of 0.61) was obtained for 3 Gy in the irradiation+PBS group. In contrast, the frequency of micronuclei increased in a dose dependent manner in both irradiation+PBS and irradiation+ADR groups. A significant elevation in the frequency of micronuclei was observed in the latter when compared with the former group. The dose response for both groups was linear quadratic. The cell proliferation indices also showed a dose dependent decline in both the groups. The decline in the cell proliferation was significantly higher in the irradiation+ADR group when compared with the irradiation+PBS group. A close correlation between the cell survival and micronuclei induction was observed in both groups, where the cell survival declined with the elevation in the micronuclei frequency. The relationship between cell survival and micronuclei induction was linear quadratic.


Subject(s)
Cell Nucleus/drug effects , Cell Nucleus/radiation effects , Doxorubicin/pharmacology , Gamma Rays , Cell Survival/drug effects , Cell Survival/radiation effects , Dose-Response Relationship, Radiation , HeLa Cells , Humans , Micronucleus Tests , Mitotic Index/drug effects , Mitotic Index/radiation effects , Tumor Stem Cell Assay
2.
Mutat Res ; 403(1-2): 177-83, 1998 Jul 17.
Article in English | MEDLINE | ID: mdl-9726018

ABSTRACT

Pregnant females appear to have an increased chromosomal sensitivity to gamma-irradiation. This hypersensitivity was found to parallel the increase of gestation hormone amounts [M. Ricoul, L. Sabatier, B. Dutrillaux, Increased chromosome radiosensitivity during pregnancy, Mutat. Res. 374(1997) 73-78]. An in vitro experiment was developed to study the effect of progesterone. We performed irradiations of whole blood from normal human donors and chromosome were analysed in first generation metaphases. By comparison to untreated controls, all cultures in which progesterone was added around the 24th h of culture exhibited an increased frequency of chromosome rearrangements, principally dicentrics and rings, which confirms the role of progesterone in the results of in vivo studies. BrdU incorporation studies suggested that progesterone was particularly efficient just before the entry into S-phase, which corresponds to the G1/S transition period. Cultures with an increased frequency of chromosome breakage had a slightly higher mitotic index than controls. It is suggested that progesterone may stimulate DNA repair in cells which reached the end of G1-phase with unrepaired breaks. This would allow the cells to enter the S-phase and survive, although some illegitimate repair leads to chromosome rearrangements, visible at the following metaphase.


Subject(s)
Chromosome Breakage , Progesterone/pharmacology , Radiation Tolerance/drug effects , Blood Cells/drug effects , Blood Cells/radiation effects , Blood Cells/ultrastructure , Female , G1 Phase/drug effects , G1 Phase/genetics , G1 Phase/radiation effects , Humans , In Vitro Techniques , Microscopy, Fluorescence , Mitotic Index/drug effects , Mitotic Index/radiation effects , Mutation , Pregnancy , Progesterone/administration & dosage , S Phase/drug effects , S Phase/genetics , S Phase/radiation effects
3.
Mutat Res ; 401(1-2): 33-7, 1998 Jun 05.
Article in English | MEDLINE | ID: mdl-9639669

ABSTRACT

The present paper describes an in vivo micronucleus assay using Cytochalasin B (CyB). Mice bearing three different tumours, fibrosarcoma (Swiss albino mice), B16 F1 melanoma (C57 BL) and Ehrlich ascites carcinoma (Swiss albino mice), were injected with repeated doses of CyB at different time intervals and binucleate cells were scored at 24, 36, 48, 60 and 72 h after CyB injection. It was found that three doses of 3+2+2 mg/kg CyB administered intraperitoneally (i.p.) at 12-h intervals effectively blocked cytokinesis. The maximum number of binucleated cells (BNC) was scored at 60 h after the last CyB dose. This dose schedule was also effective in scoring micronuclei in BNC after irradiation.


Subject(s)
Cell Division/drug effects , Cytochalasin B/toxicity , Micronucleus Tests/methods , Analysis of Variance , Animals , Carcinoma, Ehrlich Tumor/genetics , Carcinoma, Ehrlich Tumor/pathology , Cell Division/radiation effects , Cobalt Radioisotopes , Female , Fibrosarcoma/genetics , Fibrosarcoma/pathology , Gamma Rays , Male , Melanoma, Experimental/genetics , Melanoma, Experimental/pathology , Mice , Mice, Inbred C57BL , Mitotic Index/drug effects , Mitotic Index/radiation effects
4.
Eur J Surg Oncol ; 24(3): 169-73, 1998 Jun.
Article in English | MEDLINE | ID: mdl-9630854

ABSTRACT

AIMS: To investigate the use of pre-operative chemo-irradiation in downstaging advanced rectal cancer prior to surgical resection. METHODS: We examined the pathological effects of chemo-irradiation on 24 rectal tumours and correlated the efficacy of treatment with the level of apoptosis, mitosis, P53 and bcl-2 protein expression on pre-treatment biopsies. RESULTS: All tumours were resectable following chemo-irradiation. Six cancers showed complete regression with no viable tumour in the resection specimen. A significant correlation was found between spontaneous tumour apoptosis and tumour regression. CONCLUSIONS: Our results suggest that in rectal cancer the apoptotic rate in untreated tumour tissue may predict sensitivity to radiation and cytotoxic agents. No relationship was found between regression and mitotic rate, p53 or bcl-2 expression.


Subject(s)
Adenocarcinoma/pathology , Adenocarcinoma/therapy , Apoptosis/drug effects , Apoptosis/radiation effects , Gene Expression Regulation, Neoplastic/drug effects , Gene Expression Regulation, Neoplastic/radiation effects , Proto-Oncogene Proteins c-bcl-2/metabolism , Rectal Neoplasms/pathology , Rectal Neoplasms/therapy , Tumor Suppressor Protein p53/metabolism , Adenocarcinoma/drug therapy , Adenocarcinoma/physiopathology , Adenocarcinoma/radiotherapy , Chemotherapy, Adjuvant , Humans , Mitotic Index/drug effects , Mitotic Index/radiation effects , Radiotherapy, Adjuvant , Rectal Neoplasms/drug therapy , Rectal Neoplasms/physiopathology , Rectal Neoplasms/radiotherapy
5.
Clin Cancer Res ; 4(3): 677-82, 1998 Mar.
Article in English | MEDLINE | ID: mdl-9533537

ABSTRACT

We previously proposed a new assay using the cytokinesis-block micronucleus (MN) technique to estimate the fraction of cells undergoing mitosis in vitro [dividing fraction (DF)], potential doubling time (Tpot), and radiosensitivity (in terms of MN frequency) of human tumors. In the present study, we applied this technique to primary lung cancers to evaluate their biological characteristics, and the assay results for the proliferative activity were compared with the treatment outcome. Tumor tissues were disaggregated to single cells, which were cultured in the presence of cytochalasin B after (or without) radiation. At intervals, the proportion of multinucleate cells (its maximum value is the DF), the average number of nuclei/cell, and MNs in binucleate cells were scored. The Tpot was the extrapolated time for the nuclei:cell ratio to reach 2.0. Of the 71 tumor samples obtained, the DF and Tpot were evaluable in 61 (86%), and the MN frequency was evaluable in 52 (73%). The median DF and Tpot values were 23% and 7.7 days, respectively, for adenocarcinoma (n = 41), 26% and 8.9 days for squamous cell carcinoma (n = 13), 27% and 6.5 days for large cell carcinoma (n = 3), and 30% and 7.0 days for small cell carcinoma (n = 4). There was no significant difference in the mean DF or Tpot values according to the histological type or disease stage. The mean MN frequency after 2 Gy of radiation (minus the 0 Gy frequency) was 0.15 for adenocarcinoma, 0.17 for squamous cell carcinoma, 0.16 for large cell carcinoma, and 0.20 for small cell carcinoma. The MN frequency after radiation was positively correlated with both the DF and the baseline (at 0 Gy) MN frequency. In non-small cell lung cancer, a DF above the median was associated with an increased recurrence rate after operation, and the Tpot was correlated with the time until relapse in patients who developed recurrence. Although the clinical significance of the MN frequency needs to be clarified in future studies, the DF and Tpot determined by this assay appear to be good parameters of tumor proliferative activity.


Subject(s)
Lung Neoplasms/pathology , Micronuclei, Chromosome-Defective/radiation effects , Micronucleus Tests , Mitotic Index/radiation effects , Adenocarcinoma/pathology , Aged , Carcinoma, Large Cell/pathology , Carcinoma, Small Cell/pathology , Carcinoma, Squamous Cell/pathology , Cell Cycle/radiation effects , Cell Division/radiation effects , Disease-Free Survival , Female , Humans , Male , Micronuclei, Chromosome-Defective/pathology , Middle Aged , Neoplasm Staging , Regression Analysis , Tumor Cells, Cultured
6.
Mutat Res ; 422(1): 191-9, 1998 Nov 09.
Article in English | MEDLINE | ID: mdl-9920445

ABSTRACT

The effects of green and black tea consumption on the early indices of UVB and UVA + B skin damage in hairless mice have been studied in the absence of any chemical tumour initiators or promoters. Black tea consumption was associated with a reduction in the number of sunburn cells in the epidermis of mice 24 h after UVA + B irradiation, although there was no effect of green tea. Other indices of early damage such as necrotic cells or mitotic figures were not affected. Neutrophil infiltration as a measure of skin redness was slightly lowered by tea consumption in the UVB group. Consumption of either green or black tea resulted in significantly fewer skin papillomas and tumours induced by UVA + B light, however black tea provided better protection against UVB-induced tumours than green tea. This study confirms earlier reports that tea consumption can reduce the incidence of skin cancer in hairless mice, and indicates that black tea may afford more protection against simulated solar irradiation than green tea.


Subject(s)
Anticarcinogenic Agents , Neoplasms, Radiation-Induced/prevention & control , Phytotherapy , Skin Neoplasms/prevention & control , Skin/radiation effects , Tea/therapeutic use , Ultraviolet Rays , Animals , Dose-Response Relationship, Radiation , Female , Mice , Mice, Hairless , Mitotic Index/radiation effects , Necrosis , Neoplasms, Radiation-Induced/etiology , Neutrophils/radiation effects , Skin/pathology , Skin Neoplasms/etiology
7.
Exp Hematol ; 25(11): 1167-71, 1997 Oct.
Article in English | MEDLINE | ID: mdl-9328453

ABSTRACT

In our previous studies aimed at designing appropriate strategies to accelerate recovery of the immune system after irradiation, we found that the hematopoietic cytokine recombinant murine (rmu) interleukin (IL)-3 was able to induce differentiation and growth of thymocytes and splenic T and B lymphocytes in mice exposed to x-rays (200-500 cGy). The recovery, however, was complete at 7 days only after a dose of 200 cGy, whereas 2, 3, and 4 weeks were necessary to achieve full recovery after 300, 400, and 500 cGy, respectively. These studies were extended to investigate the effects of another hematopoietic cytokine, recombinant human (rhu) IL-11, a bone marrow stromal-derived cytokine, administered together with IL-3 to irradiated mice. The synergistic effect of the two cytokines was evident when relatively small doses of rhu IL-11 were injected with an optimal dose of rmu IL-3.


Subject(s)
B-Lymphocytes/radiation effects , Interleukin-11/pharmacology , Interleukin-3/pharmacology , T-Lymphocytes/radiation effects , Whole-Body Irradiation , Animals , B-Lymphocytes/drug effects , B-Lymphocytes/immunology , Bone Marrow Cells/drug effects , Bone Marrow Cells/radiation effects , CD4-Positive T-Lymphocytes/radiation effects , CD8-Positive T-Lymphocytes/radiation effects , Cell Cycle/drug effects , Cell Cycle/radiation effects , Cytokines/pharmacology , Dose-Response Relationship, Radiation , Hematopoiesis/radiation effects , Humans , Male , Mice , Mice, Inbred C57BL , Mitotic Index/drug effects , Mitotic Index/radiation effects , Recombinant Proteins/pharmacology , Spleen/drug effects , Spleen/immunology , Spleen/radiation effects , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , Thymus Gland/drug effects , Thymus Gland/immunology , Thymus Gland/radiation effects , X-Rays
8.
Int J Radiat Biol ; 72(4): 423-33, 1997 Oct.
Article in English | MEDLINE | ID: mdl-9343107

ABSTRACT

High linear energy transfer (LET) particles are more efficient than sparsely ionizing radiations in inducing chromosomal aberrations, in particular complex rearrangements. We analysed R-banded chromosome rearrangements in human lymphocytes irradiated with several ions having a wide range of LET (31.3-1435 keV/micron). The frequency of chromosome breaks unrejoined or inferred from observed rearrangements, and of complex rearrangements induced by a single particle, increased with the LET up to about 100-150 keV/micron and seemed to level off for higher LET values. Additional study was focused on damage induced by oxygen ions of three different energies. Significant cell cycle delay, and multiple chromosome rearrangements and breaks were demonstrated using Giemsa and Fluorescence-plus-Giemsa stainings, coupled with chromosome painting. Damage increased with the fluence and the LET, but at the higher LET damage decreased for fluences > 10(7) particles/cm2. Cell death and G2 block might be involved in this phenomenon. Chromosome 1 painting exhibited a high frequency of breaks and complex rearrangements, which would not have been detected using a standard staining. Complex rearrangements were induced by as few as one particle per cell nucleus and may be considered as a biological fingerprint of high-LET irradiation.


Subject(s)
Chromosome Aberrations , Chromosomes, Human/radiation effects , Lymphocytes/radiation effects , Lymphocytes/ultrastructure , Azure Stains , Cell Cycle/radiation effects , Humans , In Situ Hybridization, Fluorescence , Ions , Linear Energy Transfer , Lymphocytes/cytology , Mitotic Index/radiation effects , Oxygen/chemistry , Staining and Labeling/methods
9.
Int J Radiat Biol ; 71(1): 41-9, 1997 Jan.
Article in English | MEDLINE | ID: mdl-9020962

ABSTRACT

The relationship between chromosomal breakage and perturbations of cell cycle progression was investigated in lymphoblastoid cell lines established from a healthy donor, two subjects affected by Nijmegen Breakage Syndrome (NBS) and an ataxia-telangiectasia (AT) patient. The cytogenetic analysis revealed a similar chromosomal hypersensitivity in both NBS and AT cells exposed in the G1 phase to 200 cGy X-rays or in G2 to 15-30 cGy. Similarly, no differences were observed in the frequency of chromatid-type aberrations induced in G2 by 1-2 pg/ml calicheamicin gamma 1I, a DNA double-strand break inducer. In addition, as observed in AT cells, the rate of G2 radiation-induced chromosomal damage was less enhanced in NBS than in control cells following 3-h incubation with inhibitors of DNA synthesis/repair (cytosine arabinoside, aphidicolin, DMSO, hydroxyurea, caffeine). This is suggestive of an altered DNA lesion-processing pathway common to both syndromes. Despite the close resemblance of cellular phenotypes in the two syndromes, the analysis of mitotic indices carried out at 2 and 4 h postirradiation indicated that NBS sustained a G2-delay greater than that observed in AT cells, Furthermore, the flow cytometric analysis of 50-300 cGy irradiated cells at 10 and 20 h before harvesting showed that NBS cells sustained a G2/M phase arrest markedly lower than AT cells. Our data indicate that NBS and AT gene products are involved in a common pathway of radiation-induced chromosomal damage, but in a different one for cell cycle control after irradiation.


Subject(s)
Ataxia Telangiectasia/genetics , Chromosome Breakage , DNA/drug effects , DNA/radiation effects , Cell Cycle/drug effects , Cell Cycle/radiation effects , Cell Line/drug effects , Cell Line/radiation effects , DNA Repair/drug effects , Flow Cytometry , Humans , Mitotic Index/radiation effects , Radiation Tolerance , Sister Chromatid Exchange , Syndrome
10.
Radiat Res ; 147(1): 1-12, 1997 Jan.
Article in English | MEDLINE | ID: mdl-8989363

ABSTRACT

The goal of the present study was to assess changes in proliferation in the mouse jejunum after irradiation and the role of the growth factors EGF, TGF-alpha and TGF-beta 1-3 in the proliferative response. Our working hypothesis was that feedback signals from the villus to cells in the crypt regulate proliferation, and that the growth factors EGF and TGF-alpha with their common receptor EGF-R are involved in stimulation of proliferation, while the growth factors TGF-beta 1-3 with their receptors TGF-beta RI and TGF-beta RII are involved in inhibition of proliferation during this regulation. Immunohistochemical detection methods and automated image analysis were used for objective quantification of growth factor expression. The data indicate that, after 5 Gy irradiation, growth stimulation in the crypts takes place before major changes in the villi are observed. However, the combination of the reduction in the cell number, the number of cells expressing TGF-beta 1-3 and the reduction in the level of expression of TGF-beta 1-3 in the villi may cause the release of crypt cells from regulatory growth inhibition and initiate a proliferation-stimulating signal by an increase in the production of TGF-alpha and EGF. Regulation of proliferation after initiation of a proliferative response seems to be related more to the growth factors EGF, TGF-alpha and TGF-beta 3 in the crypts than to villus cellularity or growth factor expression, supporting the concept of stem cell autoregulation as a mechanism of cell regeneration in the intestinal crypt.


Subject(s)
Epidermal Growth Factor/biosynthesis , ErbB Receptors/biosynthesis , Intestinal Mucosa/radiation effects , Jejunum/radiation effects , Transforming Growth Factor alpha/biosynthesis , Transforming Growth Factor beta/biosynthesis , Whole-Body Irradiation , Animals , Apoptosis/radiation effects , Feedback , Female , Gene Expression/drug effects , Immunohistochemistry , Intestinal Mucosa/cytology , Intestinal Mucosa/metabolism , Jejunum/cytology , Jejunum/metabolism , Mice , Mice, Inbred C3H , Mitosis/radiation effects , Mitotic Index/radiation effects , Time Factors
11.
J Photochem Photobiol B ; 40(3): 253-7, 1997 Oct.
Article in English | MEDLINE | ID: mdl-9372613

ABSTRACT

The influence of light emitted from a diode laser centred at lambda = 805 nm was investigated on murine skeletal myotubes (C2), normal urothelial cells (HCV29), human squamous carcinoma cells of the gingival mucosa (ZMK) and urothelial carcinoma cells (J82) in a computer-controlled irradiation chamber. Cells were treated with varying fluences between 0 and 20 J cm-2. The response was tested by analysis of the mitotic index using single cell counting after Orcein staining and proliferation index based on BrdU incorporation during DNA synthesis. While the mitotic index of C2, HCV29 and J82 cells increased at a fluence of 4 J cm-2, irradiation with fluences of 20 J cm-2 resulted in a slight decrease. ZMK tumor cells showed a decrease of the mitotic index with both fluences. No significant differences could be determined when using irradiances between 10 mW cm-2 and 150 mW cm-2. The BrdU test after irradiation showed no significant effects compared to the controls in each cell line.


Subject(s)
Lasers , Animals , Cell Line/radiation effects , DNA/biosynthesis , Epithelial Cells/radiation effects , Humans , Mice , Mitotic Index/radiation effects , Muscle, Skeletal/cytology , Muscle, Skeletal/radiation effects , Tumor Cells, Cultured/radiation effects
12.
Mutat Res ; 358(2): 155-60, 1996 Nov 04.
Article in English | MEDLINE | ID: mdl-8946020

ABSTRACT

Experiments were carried out with human lymphocytes to test whether there was any relation between the changes that conditioning treatment can produce in cell progression or in mitotic delay induced by the challenge dose and the presence of an 'adaptive response' (AR). In experiments in which the cells were successively fixed after the challenge dose, the interaction between conditioning treatment and challenge was of the same sign for all the fixation times: therefore it is likely that modifications of the cytogenetic damage in primed cells is not a mere reflection of stage sensitivity. In experiments in which using 1 Gy as conditioning treatment we induced a drastic extension of G2, we did not observe any AR; therefore, even if conditioning treatment can induce modifications in the cell-cycle phases before and/or after challenge, there is probably no link between these modifications and the presence of an AR.


Subject(s)
Adaptation, Physiological/genetics , Adaptation, Physiological/radiation effects , Lymphocytes/radiation effects , Mitosis/radiation effects , Cells, Cultured , DNA Damage/radiation effects , Dose-Response Relationship, Radiation , Female , G2 Phase/radiation effects , Humans , Lymphocytes/cytology , Male , Middle Aged , Mitotic Index/radiation effects , X-Rays
13.
Radiat Res ; 146(3): 259-66, 1996 Sep.
Article in English | MEDLINE | ID: mdl-8752303

ABSTRACT

Resistance to the lethal effects of ionizing radiation has been demonstrated in a wide variety of cell types with defects in the p53 gene (thymocytes, splenic B and T cells, in vitro hemopoietic colony-forming cells and intestinal cells of the mouse, embryo cells of the rat, and human Burkitt's lymphoma cells). In contrast, Slichenmeyer et al. (Cancer Res. 53, 4164-4167, 1993) found no evidence of resistance in fibroblasts derived from p53 null mice. The aim of our study was to compare the radiation response of hemopoietic colony-forming cells (in vitro CFC) and of fibroblastoid colony-forming cells or units (CFU-F) within the same tissue (marrow) in p53 null mice (-/-), heterozygotes (+/-) and wild-type animals (+/+). We have also tested the hypothesis that, in proliferating cells, radiation-induced cell killing is mediated through chromosome damage by examining the relationship between these end points in hemopoietic cells of the three mouse types. Both in vitro CFC and CFU-F of -/- mice were resistant to cell killing compared with +/+ and +/- mice whose cellular sensitivities were indistinguishable. The resistance was characterized by a broader "shoulder" on the cell survival curve, i.e. a higher extrapolation number but similar D0 values using the multitarget model or a lower alpha coefficient using the linear-quadratic model. The frequency of chromosomally abnormal marrow cells after irradiation was similar for the three genotypes. However, marrow cells with aberrations carried more aberrations in -/- mice than in +/+ or +/- mice such that the total number of aberrations per 100 cells was higher in -/- mice. Since there were no differences in the yields of aberrations between genotypes in spleen lymphocytes or in CFU-F (both noncycling at the time of irradiation) and less mitotic inhibition in -/- marrow cells than in +/+ or +/- cells, the chromosomal radiosensitivity of -/- marrow hemopoietic cells might be related to reduced cell cycle delay allowing insufficient time for repair, but other explanations have been considered. We postulate that the radiation resistance of both hemopoietic CFC and CFU-F in -/- mice is a consequence of the failure of DNA/chromosome damage to trigger apoptosis or permanent cell cycle arrest to the same extent as in the +/+ or +/- mice: hence the lack of correlation between chromosome damage and cell death in the three mouse types.


Subject(s)
Bone Marrow/radiation effects , Cell Death/radiation effects , Chromosome Aberrations , Gamma Rays , Genes, p53 , Hematopoietic Stem Cells/radiation effects , Tumor Suppressor Protein p53/deficiency , Analysis of Variance , Animals , Bone Marrow Cells , Burkitt Lymphoma , Cell Survival/radiation effects , Cells, Cultured , Colony-Forming Units Assay , Crosses, Genetic , Dose-Response Relationship, Radiation , Embryo, Mammalian , Hematopoietic Stem Cells/cytology , Hematopoietic Stem Cells/pathology , Heterozygote , Humans , Mice , Mice, Inbred C57BL , Mice, Knockout , Mitotic Index/radiation effects , Rats , Stem Cells , Tumor Cells, Cultured
14.
Mutat Res ; 367(4): 225-32, 1996 Apr 06.
Article in English | MEDLINE | ID: mdl-8628329

ABSTRACT

The effect of gamma ray pretreatment on sister-chromatid exchange induction by mitomycin C (MMC) was determined in murine bone marrow cells in vivo. A 30% reduction in the expected SCE frequency was observed assuming an additive effect. These results support the prediction of the replicative model for SCE formation with regard to the interactions between mutagens, and confirm previous results focused on the adaptive response.


Subject(s)
Gamma Rays , Mitomycin/toxicity , Sister Chromatid Exchange , Animals , Antibiotics, Antineoplastic/toxicity , Bone Marrow/drug effects , Bone Marrow/radiation effects , Bone Marrow Cells , Cell Division/drug effects , Cell Division/radiation effects , Cells, Cultured , Male , Mice , Mice, Inbred BALB C , Mitotic Index/drug effects , Mitotic Index/radiation effects , Mutagens/toxicity , Sister Chromatid Exchange/drug effects , Sister Chromatid Exchange/radiation effects
15.
Mutat Res ; 351(2): 193-7, 1996 Apr 13.
Article in English | MEDLINE | ID: mdl-8622714

ABSTRACT

Experiments were carried out with human lymphocytes to test the effect of low-dosage X-ray irradiation (2 cGy) on cell-cycle kinetics and on the mitotic delay induced by the conditioning pretreatment alone or by a subsequent high dose of X-ray. All the tests were performed using lymphocytes from two donors who had previously displayed considerable differences in the interaction between a low and a high dose of ionizing radiation. A dose of 2 cGy led to significant variations in mitotic indices (MI) which differed for the two donors in relation to variations in the times of irradiation and fixation after stimulation with PHA. Moreover in one of the two donors 4-6 h after challenge the pretreated cultures have a higher MI that the controls; on the other hand, conditioning treatment alone induces in the other donor an extension of both G2 and of the time taken by cells in S at the time of challenge to reach mitosis. These findings could in the future provide some insight into the problem of the variability of the adaptive response in human lymphocytes.


Subject(s)
Cell Cycle/radiation effects , Lymphocytes/radiation effects , Mitotic Index/radiation effects , Humans , Male , Middle Aged , Radiation Dosage
16.
Radiat Res ; 142(3): 276-80, 1995 Jun.
Article in English | MEDLINE | ID: mdl-7761577

ABSTRACT

Oncogenic transformation of synchronized C3H 10T1/2 cells was determined after exposure to 4.3 MeV alpha particles (LET = 101 keV/microns). Two synchronization techniques were tested using basic and modified protocols: one based on the release of cells from contact inhibition and the second on the mitotic shake-off method. Progression of cells through the cycle was followed as a function of time by flow cytometric analysis, DNA labeling for passage through S phase, the growth curve for the cell number and mitotic index measurements. The conclusion is that, although the release of cells from confluence provides higher yields of synchronized cells, mitotic shake-off proved to be the best way of collecting a synchronized population of minimally perturbed cells. Cells synchronized by mitotic shake-off were irradiated with 0.30 Gy in the interval between 2 and 10 h corresponding to G1 and early S phases. For comparison asynchronous populations were irradiated in parallel. Oncogenic transformation frequency, corrected for background, in mid-G1 phase was (18 +/- 4) x 10(-5) (average values of frequencies at 4 and 6 h) compared with the value of (8 +/- 4) x 10(-5) for the asynchronous population. While these data are suggestive of a trend toward a slightly increased sensitivity in mid-G1 phase, it is not statistically significant. The surviving fraction is constant in G1 phase.


Subject(s)
Alpha Particles , Cell Cycle/radiation effects , Cell Transformation, Neoplastic , 3T3 Cells , Animals , Cell Survival/radiation effects , Flow Cytometry , Kinetics , Mice , Mice, Inbred C3H , Mitosis/radiation effects , Mitotic Index/radiation effects , Time Factors
17.
Immunol Cell Biol ; 73(3): 239-44, 1995 Jun.
Article in English | MEDLINE | ID: mdl-7590897

ABSTRACT

The biological effect of visible light of low energy density was investigated in this study. The effects of diffuse (DL) and linearly polarized (LPL) light were compared on models in vitro and in vivo. Experiments in vitro were performed on human lymphocytes to study their blast-transformation and rosette-formation abilities. Both DL and LPL increased the number of blast-transformed cells even in a lymphocyte culture without PHA, and reduced rosette-formation of T lymphocytes. LPL had a more pronounced effect. In vivo exposure to DL and LPL of the spleens of tumour-bearing mice caused the appearance of factor(s) in their serum, inhibiting the incorporation in vitro of [3H]-thymidine into the tumour cells obtained from non-exposed animals. In the other series of experiments serum samples were taken from tumorous animals after the exposure of their spleens to LPL. Following the daily administration of these sera to another group of non-exposed tumorous mice a decreasing tendency of the mitotic kinetics of ascites tumour was observed. The application of visible (preferably linearly polarized) light for the stimulation of human immune competent cells, and clinical trials with extracorporeal irradiation of blood for the promotion of natural defences of an immune-repressed organism are suggested.


Subject(s)
Immunity, Cellular/radiation effects , Light , T-Lymphocytes/radiation effects , Adult , Animals , Cells, Cultured , Humans , Leukemia P388/metabolism , Lymphocyte Activation/radiation effects , Male , Mice , Mice, Inbred DBA , Mitotic Index/radiation effects , Rosette Formation , Spleen/radiation effects , T-Lymphocytes/metabolism , Thymidine/metabolism
18.
Cancer Res ; 55(8): 1763-73, 1995 Apr 15.
Article in English | MEDLINE | ID: mdl-7712486

ABSTRACT

The early events in the G2 checkpoint response to ionizing radiation (IR) were analyzed in diploid normal human fibroblasts (NHFs) and fibroblasts from patients with two heritable cancer syndromes. Exposure to gamma-radiation of asynchronously growing NHFs resulted in a rapid reduction in the number of cells in mitosis (G2 delay) and was accompanied by a quantitatively similar reduction in the p34CDC2/cyclin B in vitro histone H1 kinase activity as compared with sham-treated controls. This G2 delay was strong by 1 h following exposure to IR, maximal by 2 h, and was accompanied by an accumulation of tyrosine-phosphorylated p34CDC2 molecules. In contrast, fibroblasts from individuals with ataxia telangiectasia displayed significantly less reduction of the mitotic index or histone H1 kinase activity after IR. Low passage fibroblasts from individuals with Li-Fraumeni syndrome having one wild-type and one mutated p53 allele were similar to NHFs in their immediate G2 checkpoint response to IR, as were NHFs expressing the human papilloma virus type 16 E6 gene product (functionally inactivating p53) and low passage cells from p53-deficient mouse embryos. However, the p53-deficient fibroblasts were genomically unstable and became defective in their early G2 checkpoint response to IR. Furthermore, immortal Li-Fraumeni syndrome fibroblasts lacking wild-type p53 displayed an attenuated G2 checkpoint response. These results link the early events in G2 checkpoint response to IR in NHFs with a rapid inhibition of p34CDC2/cyclin B protein kinase activity and demonstrate that while not required for this immediate G2 delay, lack of p53 can lead to subsequent genetic alterations that result in defective G2 checkpoint function.


Subject(s)
Ataxia Telangiectasia/genetics , G2 Phase/genetics , Genes, p53 , Li-Fraumeni Syndrome/genetics , Ataxia Telangiectasia/pathology , Cells, Cultured , Fibroblasts/cytology , Frameshift Mutation , G2 Phase/radiation effects , Gamma Rays , Humans , Infant, Newborn , Kinetics , Li-Fraumeni Syndrome/pathology , Mitosis , Mitotic Index/radiation effects , Protamine Kinase/metabolism , Reference Values , Time Factors
19.
Acta cir. bras ; 10(1): 25-33, jan.-mar. 1995. ilus, tab, graf
Article in English | LILACS | ID: lil-155272

ABSTRACT

Foram estudados os aspcectos morfológicos da parede do íleo de camundongos da linhagem C58BL expostos aos raios X, corpo inteiro, na dose única de 154,8 mC/Kg (600 R) e também a morfometria das figuras de mitose e das células caliciformes à microscopia de luz comum. Observamos alteraçöes morfológicas intensas no epitélio da mucosa ileal no período de 24 horas após irradiaçäo, tendência a recuperaçäo às 72 horas e normalizaçäo às 144 horas. A análise morfométrica demonstrou o índice mitótico significantemente baixo (quase nulo) no período significantemente baixo (quase nulo) no período de 24 hotas depois da irradiaçäo, rebote às 72 horas e normalizaçäo do mesmo às 144 horas. O índice de células caliciformes evidenciou diminuiçäo significante no período de 72 horas após irradiaçäo e recuperaçäo às 144 horas


Subject(s)
Animals , Male , Mice , Ileum/radiation effects , Mitotic Index/radiation effects , Epithelium/pathology , Epithelium/radiation effects , Ileum/pathology , Radiation, Ionizing , Time Factors , Whole-Body Irradiation
20.
Acta cir. bras ; 9(4): 174-82, out.-dez. 1994. ilus, tab, graf
Article in Portuguese | LILACS | ID: lil-143513

ABSTRACT

Foram estudados os aspectos morfológicos da parede do ileo de camundongos da linhagem C57BL expostos aos raios X, corpo inteiro, na dose única de 154,8mC/Kg (600 R) e também a morfometria das figuras de mitose e das células calciformes à microscopia de luz comum. Observamos alteraçöes morfológicas intensas no epitélio da mucosa ileal no período de 24 horas após irradiaçäo, tendência à recuperaçäo às 72 horas e normalizaçäo às 144 horas. A análise morfométrica demonstrou o índice mitótico significantemente baixo (quase nulo) no período de 24 horas depois da irradiaçäo, rebote às 72 horas e normalizaçäo do mesmo às 144 horas. O índice de células caliciformes evidenciou diminuiçäo significante no período de 72 horas após irradiaçäo e recuperaçäo às 144 horas


Subject(s)
Mice , Animals , Male , Ileum/radiation effects , Intestinal Mucosa/radiation effects , Ileum/pathology , Mitotic Index/radiation effects , Intestinal Mucosa/pathology , Photomicrography , Time Factors
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