Biomedical subjects
Publications and source records attributed to C Fuster.
A simple new method is described for obtaining sequential and a combination of differential sister chromatid staining and G-banding in the same metaphase. Using this method the sister chromatid exchanges and chromosome lesion breakpoints can be precisely localized in particular bands of individual chromosomes.
Most Salmonella typhi isolated in Spain are susceptible to antibiotics commonly used in its treatment as chloramphenicol, ampicillin and cotrimoxazole. Three multiresistant strains have been isolated from different patients the last two years. Two phage type M1, biotype xylose tetrationate + strains were isolated from blood of two patients in Bembibre (León). One phage type E1a biotype xylose + tetrationate reductase + strain was isolated from blood and faeces of one patient in Barcelona. All strains harboured a 79 Mdal plasmid responsible for multiresistance, chloramphenicol acetyl transferase production and conjugative.
The spontaneous decondensation of constitutive heterochromatic regions of chromosomes 1, 9, 16, and Y has been observed in 46.6 per cent of chorionic villus samples. This type of decondensation is occasionally observed in amniotic fluid cells (9 per cent) and has never been found in fetal lymphocytes. The phenomenon is similar to that described in spermatogonial metaphases, in primary and secondary spermatocytes and in human sperm chromosomes, although decondensation of the heterochromatin of chromosome 15 has never been recorded in chorionic villus samples.
We have carried out cytogenetic studies, using the G-banding technique, in peripheral blood lymphocytes of 10 patients affected by breast carcinoma. The frequency of aberrant metaphases (7.36%) is significantly different from that of our laboratory controls (3.76% of aberrant metaphases) but not from that detected in patients suffering from bladder cancer (10.64%) and Hodgkin's disease (11.03%), two conditions that have previously been described as chromosomally unstable. Our results suggest that breast carcinoma patients show a degree of chromosomal instability that could be related to a predisposition to neoplastic disease.
The relationship between the presence of a high frequency of chromosome aberrations and a predisposition to cancer has been well established in the so-called chromosome instability syndromes. Chromosome instability is also present in a variety of patients affected by cancer, and sometimes in their healthy relatives. We present a cytogenetic study carried out in lymphocytes from 13 untreated bladder carcinoma patients (only four of them had a history of occupational exposure to mutagens). Percentages of aberrant metaphases were significantly higher in cancer patients than in controls. Of the total number of chromosome aberrations in cancer patients, 67.16% corresponded to major structural chromosome abnormalities, while 25.37% were gaps or breaks. Numerical abnormalities represented 7.46% of the total. The bands more frequently involved in chromosome rearrangements were 5q31 and 1q32. Our results tentatively indicate that a significant proportion of patients with bladder carcinoma may have an underlying inherent chromosome instability. An age effect cannot be excluded, but we did not find significant differences between patients over 50 years of age and patients under 50 years of age.
Telomere association of chromosomes of a phenotypically and mentally normal individual was detected in 11.7% of metaphases cultured in RPMI-1640 with aphidicolin. No preferential involvement of any chromosome pair was detected. In two other individuals the frequency of telomere associations was much lower (1.9% and 0.7% respectively) under the same culture conditions. In the first individual the high number of telomere associations in cultures with aphidicolin along with the presence of telomere association (2.4%) in cultures with F.10 medium alone could reflect a constitutional telomere anomaly that is more often expressed in the presence of aphidicolin.
To evaluate the reliability of the quantitative extrapolation of the long-term effect of cancer therapies from somatic cells to germ cells, we compared the frequency of chromosome abnormalities in 303 lymphocytes from four individuals treated with radio- and/or chemotherapy 5-18 years earlier with the frequency in 422 spermatozoa from the same individuals. The mean frequency of structurally abnormal complements was much higher in germ cells than in somatic cells (P = 2.08 x 10(-6)). The fact that spermatogenic cells share cytoplasm is suggested as a possible factor in the increased viability of germ cells with chromosome aberrations. In addition, in spermatozoa the incidence of structural chromosome abnormalities was much higher in treated individuals than in controls (P less than 0.00060), while in lymphocytes no statistically significant differences could be observed. This observation and the apparent lack of relationship between individual frequencies in the two kinds of cells suggest that the long-term effect of anti-tumor treatments on germ cells cannot be extrapolated from the analysis of somatic cells.
The frequency and types of chromosome aberrations induced by ionizing radiation in cancer patients were evaluated in 24 cases studied just before and immediately after radiotherapy. The incidence of aberrant metaphases prior to treatment was 9.98% and increased significantly after treatment to 32.8%. The frequency of chromosome aberrations before radiotherapy was, with the exception of the cases of breast cancer and seminoma, significantly higher than that in our laboratory controls. A comparison of chromosome abnormalities observed before and after treatment indicated that dicentric translocations, rings, and reciprocal translocations increased by a factor of 23, 13, and 11, respectively, after radiotherapy. Ionizing radiation produces more asymmetrical than symmetrical chromosome aberrations and more two-break than one-break anomalies.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Recently, it has been suggested that an association exists between breakpoints involved in constitutional rearrangements and fragile sites; however, statistical analyses of this relationship are controversial. We have analyzed 1200 breakpoint from different constitutional rearrangements, 1522 breakpoints with respect to their recurrence and 217 breakpoints from sperm chromosomes as reported by several authors. The coincidence between breakpoints and fragile sites was 35.3%, 43.6% and 41.9% respectively. The statistical significance of these coincidences depends on whether factors such as the relative length of the bands or the recurrence of the rearrangements are taken into account.
Sperm and lymphocyte chromosome studies in a normal, fertile male have shown a high degree of coincidence between chromosome lesions and fragile sites in both types of cells. In this donor we also found that some fragile sites expressed in sperm chromosomes coincided with those expressed in lymphocyte chromosomes. These results indicate that the chromosome lesions expressed in sperm do not occur at random and that they are not technical artifacts. The fragility expression in sperm chromosomes could reflect in vivo conditions. The presence in some sperm metaphases of acentric fragments suggests that chromosome fragility can result in the loss of chromosome fragments or give rise to de novo structural rearrangements. However, the incidence of sperm with chromosomal abnormalities observed in this man was within the normal range.
The expression of folate-sensitive fragile sites (FS) was analyzed using MTX as a fragility inducer in seven normal subjects [four unrelated persons and three members of one family (father, mother, and son)]; a woman heterozygous for fra Xq27.3 with a 47,XXX karyotype; and her son, affected by the fra-X syndrome. The mean expression of chromosome lesions (CL) other than Xq27.3 was 70.1% (686CL in 978 metaphases), and the coincidence between CL and FS was 68.9%. We propose six new c-fra sites: bands 4q33 and 11q22 because they were found in two members of the same family; band 13q32 because it had a frequency of expression of 3% of metaphases; and bands 3p13, 8q21, and Xq21 because they were observed in four of the nine individuals studied.
A total of 660 breakpoints were identified in the chromosome aberrations detected in lymphocytes from cancer patients after radiotherapy. The results show that chromosomes 1, 3, and 7 were significantly more affected than other chromosomes by ionizing radiation in vivo. Chromosome arms 1p, 1q, 7q, and 11p were also significantly more affected. Some bands also showed a special sensitivity to radiation, and band 1q32 was the most affected. This band is proposed as a "hot point" for the clastogenic effect of ionizing radiation. A significant clustering of breakpoints in G bands was also found, especially at the telomeres, as previously described by other authors. Clustering of breakpoints was also observed in bands where fragile sites, protooncogenes, breakpoints involved in chromosomal cancer rearrangements, and breakpoints involved in chromosomal evolution of the Hominoidea are located.
In a study of the expression of folate-sensitive fragile sites in five normal individuals using RPMI medium containing methotrexate (MTX), we observed a high frequency of "sister chromatid intercrossings" (SCI) that is, the intersection of sister chromatids. The location of SCIs corresponded to fragile sites in 54.2% of the cases. Of the SCIs observed in each individual, 43%-53% were located at the same bands as their expressed fragile sites. Furthermore when RPMI + MTX medium was used instead of F-10 medium, the incidence of SCIs increased tenfold. We suggest that SCIs could indicate the existence of a pre-lesion.
The Xq27.3 fragile site was found to be expressed in an XXX woman, who was mentally and physically normal, and in her son who was mentally retarded and showed behavioural and physical features characteristic of the fragile X syndrome.
We describe the presence of a high frequency of spontaneous chromosome aberrations in lymphocytes from six untreated patients with Hodgkin's disease. The characteristics of the chromosome abnormalities observed suggest the existence of a certain degree of chromosome instability in these cases, that could be a predisposing factor for the development of malignancies.
In a study of the possible relationship between human fragile sites, chromosomal rearrangements related to neoplasia, and chromosome regions involved in evolutionary changes, we have found that 17 fragile sites related to cancer, 15 fragile sites not related to cancer, and 17 non-fragile regions also related to human malignancy correspond or are close to bands involved in rearrangements that have taken place during chromosomal evolution in primates.