Spontaneous and radiation-induced chromosomal breakage at interstitial telomeric sites

The Chinese hamster genome contains a total of 18 cytologically detectable arrays of interstitial telometic sequences. A combination of G-banding and twocolour fluorescence in situ hybridization revealed that 25 out of 27 (93%) breakpoints of spontaneously occurring terminal deletions in four immortalized Chinese hamster cell lines were located in chromosomal regions containing interstitial telomeric sequences. Each of the four immortalized Chinese hamster cell lines expressed telomerase. Radiation experiments revealed the sensitivity of interstitial telomeric sequences to radiation-induced chromosomal breakage in all telomerase-positive cell lines. However, radiation-induced chromosomal breakage at interstitial telomeric sites in non-transformed, primary Chinese hamster cells was almost non-existent. Telomerase activity in primary Chinese hamster cells was not detected. These results indirectly suggest that interstitial telomeric sites represent a favourable substrate for chromosomal healing.     

Spontaneous and radiation-induced chromosomal instability and persistence of chromosome aberrations after radiotherapy in lymphocytes from prostate cancer patients

The aim of the study was to compare the spontaneous and ex vivo radiation-induced chromosomal damage in lymphocytes of untreated prostate cancer patients and age-matched healthy donors, and to evaluate the chromosomal damage, induced by radiotherapy, and its persistence. Blood samples from 102 prostate cancer patients were obtained before radiotherapy to investigate the excess acentric fragments and dicentric chromosomes. In addition, in a subgroup of ten patients, simple exchanges in chromosomes 2 and 4 were evaluated by fluorescent in situ hybridization (FISH), before the onset of therapy, in the middle and at the end of therapy, and 1 year later. Data were compared to blood samples from ten age-matched healthy donors. We found that spontaneous yields of acentric chromosome fragments and simple exchanges were significantly increased in lymphocytes of patients before onset of therapy, indicating chromosomal instability in these patients. Ex vivo radiation-induced aberrations were not significantly increased, indicating proficient repair of radiation-induced DNA double-strand breaks in lymphocytes of these patients. As expected, the yields of dicentric and acentric chromosomes, and the partial yields of simple exchanges, were increased after the onset of therapy. Surprisingly, yields after 1 year were comparable to those directly after radiotherapy, indicating persistence of chromosomal instability over this time. Our results indicate that prostate cancer patients are characterized by increased spontaneous chromosomal instability. This instability seems to result from defects other than a deficient repair of radiation-induced DNA double-strand breaks. Radiotherapy-induced chromosomal damage persists 1 year after treatment.     

肿瘤坏死因子α和β对电离辐射诱导细胞凋亡的效应

为探讨肿瘤坏死因子（tumor necrosis foctor)α和β（TNFα和β）对电离辐射诱发细胞凋亡的效应及其机理,采用DNA琼脂糖凝胶电泳和FACS分析等方法,观察了人肿瘤坏死因子α（hTNFα)和β（hTNFβ)对^60Co-γ射线诱发细胞凋亡的形态学,生化学变化。结果显示：hTNFα或hTNFβ均可明显抑制^60Co-γ射线诱发正常人胚肺二倍体细胞（2BS）的凋亡,而相同剂量的hTNFα能促进^60Co-γ射线诱发的人体肺腺癌细胞系A549细胞凋亡,而对另一株人体肺癌SPC细胞的效应比A549降低1倍;hTNFβ能分别增强A549和SPC的细胞凋亡频率。由此认为,hTNFα和hTNFβ均可通过调节细胞的生理生化反应来改变细胞对电离辐射的敏感性,可保护正常细胞免受辐射损伤,而增加某些肿瘤细胞对辐射的敏感性。     

Epicatechin ameliorates ionising radiation-induced oxidative stress in mouse [corrected] liver

The current study was intended to evaluate the hepatoprotective effect of Epicatechin (EC) against radiation-induced oxidative stress, in terms of inflammation and lipid peroxidation. Swiss albino mice were administered with EC (15 mg/kg body weight) for three consecutive days before exposing them to a single dose of 5-Gy (60)Co gamma (γ) irradiation. Mice were necropsied and livers were taken for immunohistochemistry, western blot analysis and biochemical tests for the detection of markers of hepatic oxidative stress. Nuclear translocation of nuclear factor kappa B (NF-κB) and lipid peroxidation were increased whereas the activities of superoxide dismutase (SOD) and catalase (CAT), reduced glutathione (GSH) content and ferric reducing antioxidant power (FRAP) were diminished upon radiation exposure compared to control. Translocation of NF-κB from cytoplasm to nucleus and lipid peroxidation were found to be inhibited whereas an increase in SOD, CAT, GSH and FRAP was observed in the mice treated with EC prior to irradiation. Thus, pre-treatment with EC offers protection against γ-radiation induced hepatic alterations.     

Spontaneous polyploidy in laboratory mice. Embryological and cytogenetic analysis]

The developmental patterns of mice with spontaneous genomic aberrations at the pre- and post-implantation embryonic stages have been studied. The frequency of spontaneous triploidy varies in different strains from 1.7 to 5.8%. Digeny is the principal cytogenetical mechanism for triploidy. The triploid embryos of all the strains under study are characterized by the total delay of development already at the blastocyst stage. The most of triploids die at the stages of neurula and beginning of active organogenesis. A few triploids are resorbed during placentation. In the CBA mice, the triploidization results in the characteristic syndrome: disproportionally reduced amniotic vesicle, hypertrophied allantoic rudiment, reduction of neural plate, absence of head folds, notochord and mesenchyme. The spontaneous tetraploidy in mice occurs very rarely and is accompanied by severe developmental defects already at the preimplantation stages.     

Absence of radiation-induced adaptive response in lymphocytes of patients with Down's syndrome]

The adaptive syndrome and response (AR) in lymphocytes from 6 patients with Down syndrome (DS) were investigated. No AR was found to occur in all cases in DS cells pre-exposed to 3 rad of X-rays in S phase of cell cycle and then irradiated with 150 rad of gamma rays in G2 whereas the chromosome aberrations yield in cells from control donors was decreased twice under such conditions of the experiment.     

Spontaneous chromosome aberrations in the oogenesis of laboratory rats]

Cytological preparations were made by Tarkovsky's method from 2335 rat oocytes obtained after an induced superodulation. The chromosomes could be counted exactly in 861 oocytes. In 797 oocytes (92.7%) euploidy (metaphase II with 21 chromosomes) and in 64 oocytes (7.5%) aneuploidy was found. 60 oocytes were hypoploid, but only 4 oocytes (0.4%) were hyperploid (with 22 chromosomes). Hypoploidy can often be due to the presence of artefacts. Probably the rate of spontaneous aneuploidy in rat oogenesis is about 0.8%, this being significantly lower than the rate of spontaneous aneuploidy in mice oogenesis.     

Spontaneous cleft palate in CF#1/Ohu mice]

We found a spontaneous cleft palate in a mouse of CF#1/Ohu (Ohu University, Japan). Further, the frequency of the spontaneous cleft palate in strains of CF#1/Jms (Institute of Medical Science, University of Tokyo, Japan) and CF#1/Jah (National Institute of Animal Health, Japan) were about 3%, respectively. The frequency and the types of spontaneous cleft palate in CF#1 were clearly different from those in A/J and CL/Fr strains which were used as model animals of lip and cleft palate. We think that CF#1 is the new animal models to analyze a cleft palate genetically and biochemically.     

Spontaneous variability in a population of Candida albicans strains]

The spontaneous variability of the populations of C. albicans strains of different genesis in the morphological properties of their colonies and in the potential of the activity of their extracellular proteolytic and phospholipid enzymes has been studied. The isolated types of colonies, differing in their morphology, have the phenotypic character of variability. Different populations of strains exhibited variability in the activity of enzymes, depending on morphological variants isolated from these populations. Selected morphological variants with high potential of their proteolytic enzymes retained stability in this property for 5 generations and can be used in medical practice for the isolation of C. albicans antigens.     

A cytogenetic analysis of the antimutagenic action of alpha-tocopherol on spontaneous and radiation-induced chromosomal mutations]

The antimutagenic effect of alpha-tocopherol at concentrations of 1-10(-5)-1-10 mcC/ml was studied with respect to spontaneous and radiation-induced chromosome mutations in Allium fistulosum L. and Vicia faba L. It is established that at these concentrations alpha-tocopherol exhibits a significant antimutagenic activity, decreasing the frequency of chromosome mutations more than by 40-50%. No changes resulting from the antimutagenic effect of alpha-tocopherol were observed in the spectrum of structual mutations of chromosomes.     

Farnesylated RhoB inhibits radiation-induced mitotic cell death and controls radiation-induced centrosome overduplication

Our previous results demonstrated that expressing the GTPase ras homolog gene family, member B (RhoB) in radiosensitive NIH3T3 cells increases their survival following 2 Gy irradiation (SF2). We have first demonstrated here that RhoB expression inhibits radiation-induced mitotic cell death. RhoB is present in both a farnesylated and a geranylgeranylated form in vivo. By expressing RhoB mutants encoding for farnesylated (RhoB-F cells), geranylgeranylated or the CAAX deleted form of RhoB, we have then shown that only RhoB-F expression was able to increase the SF2 value by reducing the sensitivity of these cells to radiation-induced mitotic cell death. Moreover, RhoB-F cells showed an increased G2 arrest and an inhibition of centrosome overduplication following irradiation mediated by the Rho-kinase, strongly suggesting that RhoB-F may control centrosome overduplication during the G2 arrest after irradiation. Overall, our results for the first time clearly implicate farnesylated RhoB as a crucial protein in mediating cellular resistance to radiation-induced nonapoptotic cell death.     

Spontaneous level of sister chromosome exchanges and their distribution in human cells]

Blood of practically healthy donors of both sexes (27 females and 23 males) was cultured under the standard conditions during 96 hours. Bromodeoxyuridine (BUdR) was added at the final concentration of 10 mkg/ml 28 hours before harvesting. The slides were stained with acridine orange and Giemsa for differential staining of chromatids. In each culture sister chromatid exchanges (SCE) were analysed in 50 cells, and the part of cells undergoing the first, second and third mitoses at the time of harvesting, was calculated. According to the mean number of SCE per cell, the distribution of individuals was consistent with the normal law, the mean being 6.525 and standard deviation--0.956. A significant heterogeneity in the speed of cell cycle of cultures was observed. The coefficient of variation for the part of cells undergoing the first mitosis was 50%, for the cells in the second mitosis--15%, and for the cells in the third mitosis--154%. Correlation analysis showed a positive dependence of the mean level of SCF upon the age of a donor and upon the part of cells in the second mitosis in this individual. No reliable correlation of the SCE level with the donor's sex was observed. The distribution of cells, obtained from the culture of one individual, was best approximated by beta-distribution, and the distribution of cells obtained from the cultures of different individuals--by gamma-distribution. In both there was obtained a satisfactory approximation by Pearson's distribution of the 1 type, and significant deviations were found from the normal, Poison's and the negative binomial distribution. The conditions were found of similarity of empirical distribution of SCE in cells to the normal one. For that, it is not the value of SCE for a separate cell that should be used as a unit of measurement, but the mean from the values of frequencies for 5-10 cells. Hence, it was shown that for the evaluation of the mean frequency of SCE with the precision of 1 exchange in separate individuals it is necessary to analyse 40 cells, and to observe the 15% increase of spontaneous SCE level under the action of deleterious factors--8 individuals are enough to analyse.     

Spontaneous fluctuations in the activity of rabbit skeletal muscle NAD-kinase]

Spontaneous fluctuations in the time of the activity of the 280-300-fold purified NAD-kinase preparation from rabbit skeletal muscle following its dilution are described. Defrosted but undiluted enzyme preparation failed to exhibit any fluctuations in its activity.     

Spontaneous rosette forming, Fc and complement receptor bearing lymphocytes in pediatric diseases]

Investigations with lymphocyte subpopulations were made in 51 children aged from 1-14 years with infections of the upper airways, with acute leukaemias, and other malignant diseases. T-lymphocytes were registered by means of the spontaneous rosette test. The attempt of proving B-lymphocytes was made by means of an EAC test with human erythrocytes, anti-D-immunoglobulins and human complement. The results were compared with those obtained by an EAC test with sheep erythrocytes, sheep haemolysin and mice complement and the significance of complement discussed.     

Spontaneous frequency of micronuclei in peripheral blood lymphocytes of Kiev residents]

The level of micronuclei in the peripheral blood lymphocytes of Kyiv residents and its dependence on age, sex and smoking status were studied. Analysis of lymphocytes of 102 healthy Kyiv residents showed that the spontaneous frequency of micronuclei in individuals at the age of 21 to 67 (mean age of 42.6) was 10.5 +/- 0.5@1000. The frequency of micronuclei depends on individual age and increases by 3% per year, and also depends on smoking habits (the micronucleus frequency in smokers was 1.3 times higher then nonsmokers). There is no dependence of the micronucleus frequency on the sex of persons.