PubMed Health⌕ Search

Biomedical subjects

R Miró

Publications and source records attributed to R Miró.

At least 55 records · Page 3Linked to original sources

Repair of human sperm chromosome aberrations in the hamster egg.

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.

Animals↗

Induction of premature centromere division affecting all chromosomes under culture conditions of fragile site expression.

In a study of chromosome fragility carried out under folate and thymidine deficiency conditions, we observed a seven- to ninefold increase of the incidence of premature centromere divisions (PCDs) affecting all chromosomes. This early separation of centromeres is clearly a culture effect and distinct from PCD and centromere splitting (CS), which imply a defect in the centromere of one or more chromosomes.

Cells, Cultured↗

A method to extract DNA for molecular studies from cells fixed in Carnoy.

We describe a simple method for isolation of high-molecular-weight DNA from cells fixed in Carnoy's solution for cytogenetic studies. DNA samples were extracted from NIH3T3 cells, and no apparent degradation was noticed. This method should be useful for molecular analysis of cells fixed for cytogenetic studies.

3T3 Cells↗

Heterochromatin decondensation in chromosomes from chorionic villus samples.

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.

Age Factors↗

Chromosomal instability in breast cancer patients.

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.

Adult↗

Trisomy 7 may be a primary change in noninvasive transitional cell carcinoma of the bladder.

We describe two cases of transitional cell carcinoma of the bladder associated with trisomy 7. In one of them, trisomy 7 was the only chromosome abnormality observed. In the second case, trisomy 7 was found in 25 (80.6%) of the metaphases; in two of them this was the only anomaly, while in three metaphases trisomy 8 was also present, and in other two trisomy 10 was also observed. Our results suggest that trisomy 7 could be a primary change in TCC, and a review of the literature indicates that when it is present as the sole karyotypic abnormality is may be associated with a non-invasive behavior of the tumor.

Aged↗

Chromosome instability in bladder carcinoma patients.

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.

Adult↗

Centromere splitting in bladder cancer.

Cytogenetic studies on a bladder carcinoma, carried out using short time cultures, showed centromere splitting (CS) mainly affecting chromosomes 22, 13, 14, 21, 15, 20, 12, 7, 17, and 18. Clonal trisomies and monosomies were also detected. Our case is the first description of CS in bladder tumor cells. Our results suggest that CS is an early phenomenon in the karyotypic evolution of this case; it can be considered a primary, yet unspecific, chromosome change related to aneuploidy in bladder cancer.

Aneuploidy↗

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

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.

Antineoplastic Agents↗

Telomere association of chromosomes induced by aphidicolin in a normal individual.

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.

Aphidicolin↗

Lymphocyte and sperm chromosome studies in cancer-treated men.

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.

Antineoplastic Combined Chemotherapy Protocols↗

Human sperm chromosomes. Long-term effect of cancer treatment.

The long-term cytogenetic effect of radio- or chemotherapy or both on male germ cells was evaluated by study of the chromosomal abnormalities in spermatozoa of four men treated for cancer 5-18 years earlier. The cytogenetic analysis of 422 sperm metaphases showed no differences in the aneuploidy rate. The incidence of structural chromosome aberrations was 14.0%, however, which is much higher than in controls. Thus, the high incidence of structurally aberrant spermatozoa observed in our long-term study indicates that antitumoral treatments affect stem-cell spermatogonia and that aberrant cells can survive germinal selection and produce abnormal spermatozoa.

Antineoplastic Agents↗

Cytogenetic effects of radiotherapy: frequency and types of chromosome aberrations.

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.

Adult↗

Sperm chromosome studies in individuals treated for testicular cancer.

Sperm chromosome studies have shown that patients treated with chemotherapy for testicular cancer have a much higher incidence of chromosome abnormalities than patients treated for other types of cancer or than controls. In two out of four cases, penetration of zona-free hamster eggs was close to zero, indicating that after 2-7 years after treatment the functional capacity of the sperm had not been recuperated. The cytogenetic study of the spermatozoa shows that many of the abnormalities observed corresponded to structural aberrations that may not have a pathogenic effect in the production of abortions or of children with chromosome abnormalities.

Adult↗

Fragile sites and breakpoints in constitutional rearrangements and in human sperm chromosomes.

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.

Chromosome Aberrations↗

Expression of fragile sites in human sperm and lymphocyte chromosomes.

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.

Adult↗