Spontaneous chromosome aberrations in human somatic cells

Conclusion In conclusion it is necessary to say that at present, we cannot consider whether there may be a geographical difference in frequency of spontaneous chromosome aberrations in somatic cells. For that purpose, a very abundant experimental material is required, as well as an improvement in methodology: what causes the difference in the results of various investigators; what methodical principles should be used for collection of data.Important factors in the differences of frequencies of spontaneous chromosome aberrations are likely to be the conditions of cultivation and making the preparations, as well as the methods of scoring the chromosome aberrations. The international standardisation of the cultivation conditions and of the estimates of chromosome aberrations is needed for the further study of the rate and reasons of the spontaneous mutation process in somatic cells.     

Liposomes induce chromosome aberrations in human cultured cells

The genotoxic effect of multilamellar lipid vesicles (MLV) was analysed on cultured heteroploid and diploid human cells. Dose-dependent reduction of cell survival and mitotic rate as well as induction of chromosome aberrations were observed. Chromatid and chromosome breaks and chromatid exchanges were found in 24-h culture after liposome treatment, whereas chromosome rearrangements were prevalent at 48 h. Neutral (PC/Chol) and positive (PC/SA) MLV showed a greater damage than negative (PS/PC; PS) MLV. Fibroblasts were the most sensitive cell type. In the case of PC/Chol MLV vesicles, control experiments with PC and Chol of controlled purity ruled out the possibility that the observed chromosome aberrations were caused by toxic oxidation products present in commercial preparations.     

Significance of structural chromosome aberrations in human sperm: analysis of induced aberrations

Summary A significant increase in the incidence of structural chromosome anomalies has been observed in the sperm of patients treated with radio and/or chemotherapy for different types of cancer when analyzed by the interspecific fertilization of hamster eggs. The analysis of these aberrations shows that while in controls only 9.4% of structural abnormalities are of the stable type, in treated patients this figure increases to 39.3%, thus indicating that the anomalies have not been produced during the fertilization of the hamster egg. However, it is possible that part, or even most, of the breaks appear as a result of a reduced repair capacity of sperm chromosomes in the cytoplasm of the hamster egg.     

Radiation- and chemical-induced structural chromosome aberrations in human spermatozoa

An apoptotic phenotype induced by oxygen radicals or Bax expression has been observed in Saccharomyces cerevisiae yeast cells by electron and fluorescence microscopy. In this work, we analyzed DNA content and cellular morphology of S. cerevisiae after H(2)O(2) or UV treatment by TdT-mediated dUTP nick end labeling (TUNEL)-test and flow cytofluorimetry. A TUNEL-positive phenotype was observed in both cases, on the same samples a dose-dependent increase in the sub-G(1) population was pointed out by flow cytometry. Sub-G(1) cells were isolated by flow sorting and analyzed by electron microscopy. This population showed condensed chromatin in the nucleus and cell shrinking. This paper reports the first evidence of apoptosis in yeast cells induced by DNA damage after UV irradiation.     

Dose-response relationship for chromosome aberrations induced by fecapentaene-12 in human lymphocytes

Chromosome analyses were carried out in human lymphocytes exposed to a synthetic racemic all-trans fecapentaene-12 at 2-24 microM. A dose-dependent increase of the incidences of chromatid-type changes with distinct saturation at higher doses could be observed. The results reveal for the first time that fec-12 is a potent direct-acting mutagen in human lymphocytes.     

RBE of thermal neutrons for induction of chromosome aberrations in human lymphocytes

The induction of chromosome aberrations in human lymphocytes irradiated in vitro with slow neutrons was examined to assess the maximum low-dose RBE (RBE_M) relative to ⁶⁰Co γ-rays. For the blood irradiations, cold neutron beam available at the prompt gamma activation analysis facility at the Munich research reactor FRM II was used. The given flux of cold neutrons can be converted into a thermally equivalent one. Since blood was taken from the same donor whose blood had been used for previous irradiation experiments using widely varying neutron energies, the greatest possible accuracy was available for such an estimation of the RBE_M avoiding the inter-individual variations or differences in methodology usually associated with inter-laboratory comparisons. The magnitude of the coefficient α of the linear dose–response relationship (α = 0.400 ± 0.018 Gy^?1) and the derived RBE_M of 36.4 ± 13.3 obtained for the production of dicentrics by thermal neutrons confirm our earlier observations of a strong decrease in α and RBE_M with decreasing neutron energy lower than 0.385 MeV (RBE_M = 94.4 ± 38.9). The magnitude of the presently estimated RBE_M of thermal neutrons is—with some restrictions—not significantly different to previously reported RBE_M values of two laboratories.     

Heterochromatin and chromosome aberrations

The chromosome breaking effect of mitomycin C, methyl methanesulfonate, maleic hydrazide, 8-ethoxycaffeine and gamma rays on the primary root meristematic cells of Nigella damascena was studied. All the agents tested except 8-ethoxycaffeine, produced relatively fewer aberrations, when compared to Vicia faba cells, though both the species have nearly similar total chromosomal length. Test for the presence of heterochromatin in Nigella gave negative results and it is interpreted that the observed differences between Vicia and Nigella are due to the presence and absence of heterochromatin in their chromosome complements respectively. The role of heterochromatin in the production of chromosome aberrations and its significance in evolution are briefly discussed.     

Repair of human sperm chromosome aberrations in the hamster egg

Summary In order to study the repair capacity of fertilized hamster eggs for the lesions present or induced in human sperm, we have examined the potentiating effect of caffeine, a DNA repair inhibitor, on the frequency and types of sperm chromosome aberrations. Sperm samples were donated by an individual treated with chemotherapy for a testicular cancer 3 years previously. Exposure of spermatozoa and inseminated oocytes to caffeine led to an increase of sperm chromosome aberrations, indicating that the damage to human sperm can be repaired in untreated hamster egg cytoplasm. The potentiating effect of caffeine was mainly reflected in an increase of unrejoined aberrations, indicating that the formation of chromosomal rearrangements is also inhibited. Since both chromatid-type and chromosome-type aberrations increase after treatment with caffeine, damage to human sperm can probably be repaired inside the hamster egg cytoplasm by pre and post-replication repair mechanisms.     

Viral infectious and chromosome aberrations in Bank Vole from natural and laboratory populations]

The frequency of chromosome damage was studied in the carriers of virus of the hemorrhagic fever with renal syndrome (Puumala virus) and in noninfected animals from two laboratory colonies and two natural populations of bank vole. In the laboratory colony, where Puumala virus persisted for three years, multiaberrant ("rogue") cells were found in the bone marrow; the mean frequencies of both structural and numeral chromosome abnormalities were significantly enhanced. In the other laboratory colony, no Puumala virus was detected during all 30 years of its existence, but the mean frequencies of structural chromosome damage were increased to the same degree probably due to the prolonged breeding under laboratory conditions, which resulted in suppression of immunity and DNA repair. The voles from the natural populations were more resistant to the clastogenic viral effect, but they also had multiaberrant cells which served as indicators of viral infection. The data obtained support the hypothesis that viral infections increase mutation rate, contributing thereby to the evolution process.     

Induction of chromosome aberrations in cultured human lymphocytes treated with ethoxyquin

The chromosomal aberration test was employed to investigate the effect in vitro of a known antioxidant and food preservative, ethoxyquin (EQ, 1,2-dihydro-6-ethoxy-2,2,4-trimethylquinoline) on human chromosomes. The studies were undertaken because there are no published in vitro data on genotoxicity of EQ in mammalian cells and there are many reports pointing out that it may be harmful to animals and human beings. Lymphocytes obtained from three healthy donors were incubated with EQ (0.01–0.5 mM) both with and without metabolic activation. Stability studies performed by HPLC analysis showed that EQ was stable under the conditions of the lymphocyte cultures. The results of the chromosome aberration assay showed that EQ induces chromosome aberrations: gaps and breaks as well as dicentrics and atypical translocation chromosomes.     

Induction of chromosome aberrations in cultured human lymphocytes treated with ethoxyquin

The chromosomal aberration test was employed to investigate the effect in vitro of a known antioxidant and food preservative, ethoxyquin (EQ, 1,2-dihydro-6-ethoxy-2,2,4-trimethylquinoline) on human chromosomes. The studies were undertaken because there are no published in vitro data on genotoxicity of EQ in mammalian cells and there are many reports pointing out that it may be harmful to animals and human beings. Lymphocytes obtained from three healthy donors were incubated with EQ (0.01-0.5mM) both with and without metabolic activation. Stability studies performed by HPLC analysis showed that EQ was stable under the conditions of the lymphocyte cultures. The results of the chromosome aberration assay showed that EQ induces chromosome aberrations: gaps and breaks as well as dicentrics and atypical translocation chromosomes.     

Recurrent chromosome aberrations in cancer

Cytogenetic investigations of neoplastic cells during the past 25 years have revealed more than 600 acquired, recurrent, balanced chromosome rearrangements, and it has been established that every tumor type, studied in a sufficient number to permit conclusions, may be subdivided on the basis of specific, and even pathognomonic, abnormalities. At the molecular level, the balanced rearrangements exert their action through one of two alternative mechanisms: Deregulation of one gene by relocation to an immunoglobulin or T-cell receptor gene, or the creation of a hybrid gene by the fusion of parts of two genes. At present, nearly 100 genes have been found to be involved in neoplasia-associated chromosomal rearrangements, the great majority in hematological disorders. At the same time, the clinical usefulness of various cytogenetic abnormalities as diagnostic and prognostic aids has been increasingly appreciated. The identification of a recurring chromosome abnormality can assist in the diagnosis and subclassification of a malignant disease and, hence, in the selection of the appropriate treatment. The karyotype is also an independent prognostic factor. In hematological neoplasms, where the knowledge of chromosome abnormalities still is much more complete than is the case with solid tumors, cytogenetic analysis now plays an integral part in the diagnostic work-up of individual patients. Data obtained during recent years strongly suggest that corresponding breakthroughs will be achieved in solid tumors within a not-too-distant future.