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R Marcos

Publications and source records attributed to R Marcos.

At least 19 recordsLinked to original sources
PubMed1999

Analysis of bleomycin- and cytosine arabinoside-induced chromosome aberrations involving chromosomes 1 and 4 by painting FISH.

The genomic frequency of chromosomal aberrations obtained by chromosome painting is usually extrapolated from the observed frequency of aberrations by correcting for the DNA content of the labelled chromosomes. This extrapolation is based upon the assumption of random distribution of breakpoints from which aberrations are generated. However, the validity of this assumption has been widely questioned. While extensive investigations have been performed with ionizing radiation as chromosome breaking agent, little efforts have been done with chemical clastogens. In order to investigate interchromosomal differences in chemically-induced chromosome damage, we have used multicolour chromosome painting to analyse bleomycin-induced aberrations involving chromosomes 1 and 4, two chromosomes that differ in gene density. In addition, we have measured the effect of cytosine arabinoside upon the repair of bleomycin-induced DNA damage in chromosomes 1 and 4. Our results show that these chromosomes are equally sensitive to the clastogenic effect of bleomycin with a similar linear dose-effect relationship. However, the high gene density chromosome 1 appeared to be more sensitive to repair inhibition by Ara-C than chromosome 4. This enhanced sensitivity to repair inhibition in chromosome 1 could be mediated by preferential repair of open chromatin and actively transcribed regions.

Adult↗
PubMed1998

Biomonitoring of workers exposed to lead. Genotoxic effects, its modulation by polyvitamin treatment and evaluation of the induced radioresistance.

A population monitoring study was performed, by using the micronucleus (MN) assay in human peripheral lymphocytes, to investigate whether occupational exposure to lead is genotoxic to workers. In addition to the exposed workers group, two more groups were studied, an external group from a factory without exposure to lead and an internal control group, from the same factory as the exposed workers, but that were not directly exposed to lead. Measures of lead levels at working place and in blood were calculated, and blood samples were collected to carry out a MN study. The results from these studies indicate that the blood from workers directly exposed contained high levels of lead, compared with the other groups, and a significant increase in the frequency of both the total number of MN and the number of binucleated cells carrying MN appeared. In addition, a study on the antimutagenic effects of a polyvitamin rich diet was conducted by measuring the frequency of MN after the workers had a four month daily intake of a polyvitamin-polymineral complex. These results clearly show a significant reduction of the MN frequency evaluated after this treatment, obtaining values that were even lower than those obtained in the internal control group. Finally, a challenge assay was carried out to determine response to gamma-radiation as indication of any kind of radiosensitivity or radioresistance. The results of this experiment did not show any significant variation in the increase of the frequency of MN after challenge irradiation in the lead exposed workers; nevertheless this increase was significantly reduced in the sample obtained after the polyvitamin treatment indicating a radioresistance response.

Adult↗
PubMed1998

Lack of genotoxicity of the herbicide atrazine in cultured human lymphocytes.

The widely used herbicide atrazine was evaluated for genotoxicity in cultured human peripheral blood lymphocytes. Sister-chromatid exchanges (SCE), chromosome aberrations (CA) and micronuclei (MN) were scored as genetic endpoints. To detect eventual metabolic modification in the genotoxicity of this herbicide, the cultures of SCE and MN demonstration were also treated with S9 microsomal fraction. From our results we can conclude that atrazine was able to exert a weak cytotoxic effect. However, the overall evaluation of the genotoxicity data indicate that this herbicide is not effective in the three assays conducted, irrespective of the presence of metabolic activation, which would mean a general lack of effectiveness of atrazine to induce clastogenic and aneugenic damage in cultured human lymphocytes.

Animals↗
PubMed1998

Links between chromatin structure, DNA repair and chromosome fragility.

This paper is a brief overview of the studies we have recently conducted to unravel how chromatin structure and DNA repair modulate the fragility of diverse chromosomes and chromosomal regions. We have employed a combination of molecular cytogenetic techniques, including interphase and metaphase multicolour FISH, reverse FISH with CpG-rich probes or repaired DNA fractions, and several combinations of FISH and immunocytogenetics with antibodies against acetylated histones. The targets of our investigation were human constitutive and facultative heterochromatin, chromosomes with high and low gene density and human and hamster fragile sites. The role of DNA repair was investigated by using DNA repair deficient mutants and DNA repair inhibitors. We found that intragenomic heterogeneity in DNA repair and chromatin structure may explain a substantial part of the differential fragility of diverse chromosomes and chromosomal regions.

Animals↗
PubMed1998

[Breast cancer and heredity: results of a population case-control study in Girona].

BACKGROUND: To characterise the relationship between breast cancer and different aspects of the reproductive life, use of drugs and alcohol by family history of breast cancer. PATIENTS AND METHODS: From the cancer registry of Girona, Spain, 330 women were identified with histologically confirmed breast cancer during 1986-1989. For each case, a control woman was selected from a random sample of the population living in the matched area to the case by age (+/- 5 yr.). The information was collected by a personal interview and included: family history of breast cancer, reproductive history, presence of acne during the teenage years, use of oral contraceptives and drugs for sleep and anxiety disorders, and alcohol consumption. RESULTS: 18.5% of breast cancer cases and 8.9% of all controls had a family history of breast cancer. Family history on a first degree relative (mother or sister) was present in 10.6% of the cases and 2.8% of controls, which represented an odds ratio for breast cancer of 3.7 (95% CI, 1.8-7.8) higher than the general population. Women with a first degree family history of breast cancer were at higher risk for breast cancer if they had a history of acne during the teenage period (OR = 2.4; 95% CI, 1.1-5.2) and if they referred long menstrual periods in the early years of menarche (OR = 3.1; 95% CI, 1.3-7.0). Women with no family history had a higher breast cancer risk if they had a late menarche, long menstrual periods, late first full term pregnancy, and history of acne during puberty. Alcohol consumption and use of drugs for anxiety and sleep disorders were associated with a decreased risk of breast cancer. CONCLUSIONS: First degree family history of breast cancer seems to be the best risk indicator for developing breast cancer. Long menstrual periods and presence of acne during puberty may indicate hormonal imbalance that act independently of the family history in breast cancer development.

Adult↗
PubMed1998

The alkaline single-cell gel electrophoresis (SCGE) assay applied to the analysis of radiation-induced DNA damage in thyroid cancer patients treated with 131I.

The alkaline single-cell gel electrophoresis (SCGE or Comet) assay appears to be a promising tool for measuring DNA damage at the individual cell level in both in vitro and in vivo studies. To provide further data on the possible applicability of this assay in human biomonitoring studies, we have evaluated the eventual genetic damage induced by therapeutic exposure to 131I, by measuring the Comet length and the amount of DNA damage in peripheral blood leukocytes from a group of 28 thyroid cancer patients who received 131I sodium iodide via oral administration. Blood samples were taken just before the treatment and 1 week after it. From the results obtained after radioiodine therapy, a small increase in the Comet length and in the grade of DNA damage is observed; however, this increase is not statistically significant because of inter-individual variability and the variable responses before and after 131I treatment. Considering our previous studies showing significant increases in the frequency of cytogenetic damage (when measured as micronuclei) in patients treated with relatively low doses of 131I, the results obtained in the present work by using the Comet assay could indicate that 1 week after the exposure most of the radioiodine-induced DNA lesions, that can be detected with this assay, have already been repaired.

Adult↗
PubMed1998

Genotoxic activity of four inhibitors of DNA topoisomerases in larval cells of Drosophila melanogaster as measured in the wing spot assay.

Four inhibitors of DNA topoisomerases namely nalidixic acid, camptothecin, m-amsacrine and etoposide, have been evaluated for genotoxic effects in the wing spot test of Drosophila melanogaster. This assay assesses somatic recombination and mutational events. We studied nalidixic acid as an inhibitor of bacterial DNA gyrase, camptothecin as a topoisomerase I inhibitor, as well as m-amsacrine and etoposide as topoisomerse II inhibitors. The genotoxic effects were determined from the appearance of wing spots in flies trans-heterozygous for the recessive markers multiple wing hairs (mwh) and flare, as well as in flies heterozygous for mwh and the multiply inverted TM3 balancer chromosome. From our results it appears that whilst nalidixic acid and m-amsacrine were compounds that did not increase the incidence of mutant clones, camptothecin and etoposide proved to be significantly genotoxic in this test, being camptothecin more effective than etoposide. A significant proportion of the total spot induction was due to mitotic recombination, confirming previously reported data. On the other hand, the cotreatments of each topoisomerase inhibitor with the alkylating agent ethyl methanesulfonate (EMS) indicate that, while nalidixic acid, m-amsacrine and etoposide show a tendency to an antagonistic interaction, camptothecin shows an additive effect, suggesting mechanistic differences between the activity of the four inhibitors of DNA topoisomerases studied.

Amsacrine↗
PubMed1998

Granulomatous epididymo-orchitis: sonographic features and clinical outcome in brucellosis, tuberculosis and idiopathic granulomatous epididymo-orchitis.

PURPOSE: We reviewed and analyzed sonographic findings in granulomatous epididymo-orchitis in an attempt to differentiate this rare inflammatory entity from other causes of enlarged scrotum, such as tumors. MATERIALS AND METHODS: We retrospectively reviewed sonographic features of 9 patients a mean of 41 years old with specific and nonspecific granulomatous epididymo-orchitis, including brucellosis in 7, tuberculosis in 1 and idiopathic granulomatous epididymo-orchitis in 1. Histological confirmation was obtained in 3 cases, and in the remaining 6 positive clinical manifestations and laboratory tests for brucellosis were accepted as the main criteria for the diagnosis of brucellar epididymo-orchitis. RESULTS: The most notable echographic finding was an enlarged and heterogeneous epididymis, predominantly in the body and tail. Testicular involvement consisted of a diffusely hypoechoic testis or focal intratesticular areas. Thickening of the scrotal wall and tunica albuginea, and moderate hydrocele were also noted occasionally. Followup scans revealed intratesticular abscesses in 3 patients. CONCLUSIONS: These echographic findings may suggest the diagnosis of granulomatous epididymo-orchitis in the appropriate clinical setting, and help to avoid unnecessary orchiectomy for benign disease.

Adult↗
PubMed1998

Application of the single cell gel electrophoresis (SCGE) assay to the detection of DNA damage induced by 131I treatment in hyperthyroidism patients.

To provide further data on the possible applications of the single cell gel electrophoresis (SCGE) or Comet assay in human biomonitoring studies, we have evaluated the eventual genetic damage induced by therapeutic exposure to 131I, by measuring the tail length of the comet and the amount of DNA damage in peripheral blood cells from 16 hyperthyroidism patients treated with [131I]sodium iodide by oral administration. Blood samples were taken just before the treatment and 1 week and 1 month after. The results show a slight but significant increase in the mean tail length in the sample obtained 1 month after treatment. When the cells were classified according to the grade of damage the two post-treatment samples showed a clear increase in the proportion of damaged cells. The results of this study indicate that the DNA damage caused by 131I can be detected with the Comet assay, but when comparing the data reported here with our previous results obtained from the same patients and sampling times with the sensitive and well-established micronucleus test, the response in the Comet assay was less clear.

Adult↗
PubMed1998

Induced somatic and germinal reversion of the white-spotted-1 insertional mutant phenotype in Drosophila melanogaster.

The white-spotted-1 (Wsp1) mutant of Drosophila melanogaster is characterized by the presence of an 8.7 kb retrotransposon (B104) inserted in the regulatory region of the white locus. The frequency of reversion in both somatic tissue and the germline after exposure to three different alkylating agents has been analysed. To determine if germinal revertants were induced by precise excision of the insertional element we analysed several phenotypic revertants using PCR and Southern blot techniques. The results indicate that, under our experimental conditions, the mutagens used did not induce excision of B104 in the white gene. In addition, the revertant phenotypes obtained were due to the existence of second site modifiers acting on expression of white. Such modifiers map near the white locus and, at least in one case, may correspond to suppressor-of-white-spotted.

ATP-Binding Cassette Transporters↗
PubMed1998

Micronuclei analysis in lymphocytes of pesticide sprayers from Concepción, Chile.

To estimate the genetic risk associated with pesticide exposure in a defined population, the frequency of micronuclei (MN) in peripheral blood lymphocytes from a group of 22 pesticide sprayers from Concepción, Chile, occupationally exposed to pesticide mixtures was evaluated. After scoring 1,000 binucleated cells for each donor, no significant increases were observed either for the total number of MN or for binucleated cells with MN, when compared with a concurrent control population. In addition, when the effects of different confounding factors such as age, smoking, and drinking habits were considered, no significant effect was observed. Our conclusion is that, in this specific group of workers and under the particular conditions of exposure to pesticides, when evaluated by the micronucleus assay, no genetic risk was detected.

Adult↗
PubMed1997

Micronuclei, centromere-positive micronuclei and chromosome nondisjunction in cytokinesis blocked human lymphocytes following mitomycin C or vincristine treatment.

The influence of sampling time on the frequencies of micronuclei, centromere-positive micronuclei and chromosome nondisjunction was investigated in binucleated lymphocytes following treatment with a known clastogen (mitomycin C) or an aneuploidy-inducing agent (vincristine sulfate). Cytochalasin B (6 micrograms/ml) was added 44 h after mitogen stimulation and cultures were harvested 12, 28, 36 and 48 h thereafter. Micronucleated cells and micronuclei were significantly induced by the two treatments at all sampling times. Furthermore, in situ hybridization with an 'all centromeres' probe showed that vincristine-induced micronuclei were prevalently centromere-positive whereas in mitomycin C-treated cultures only a minor fraction of induced micronuclei contained the hybridization signals. Chromosome nondisjunction rates, as measured by in situ hybridization with chromosome 7- and 11-specific alphoid probes, significantly increased following vincristine treatment. Chromosome nondisjunction and total micronucleus frequencies were found to increase with time both in controls and in mutagen-treated cultures, whereas the percentage of centromere-positive micronuclei in the different treatments was not influenced by the sampling time. Our data suggest that even in the presence of 6 micrograms/ml cytochalasin B, the abnormal segregation of binucleated cells may contribute to the baseline level of micronuclei and influence the results obtained. The introduction of a short cytochalasin B treatment (between 12 and 28 h) in the cytokinesis-blocked micronucleus assay may avoid the cytochalasin B effect on micronucleus frequencies.

Aneuploidy↗
PubMed1997

SCE analysis in peripheral blood lymphocytes of a group of filling station attendants.

Petroleum derivatives constitute a complex mixture of chemicals which contain known genotoxicants. Thus, chronic occupational exposure to such derivatives may be considered to possess genotoxic risk. Service station attendants are workers exposed to petroleum derivatives and, as consequence, biomonitoring studies designed to evaluate the genetic risk are required. Here we present the data on sister chromatid exchange (SCE) frequencies, proliferation rate index (PRI) and cells with high frequency of SCE (HFC) from a group of 42 attendant workers. In addition, data from a group of 45 unexposed (controls) are presented. The results obtained indicate that there are no significant differences in SCE values between the exposed workers when compared to the non-exposed individuals. The only difference is found when smoking habit is considered, the smokers having significant increases in the SCE frequency. There is a slight increase in the HFC frequency of the occupationally exposed group but the difference did not attain statistical significance.

Adult↗
PubMed1997

Micronuclei induction by 131I exposure: study in hyperthyroidism patients.

To evaluate the eventual genetic damage induced by therapeutic exposure to 131I, we have studied the presence of micronuclei (MN) in binucleated peripheral blood lymphocytes from a group of 28 hyperthyroidism patients who received 131I sodium iodide, via oral administration. The study was conducted over time and blood samples were obtained before the treatment, and 1 week, 1 month and 3 months after it. The results obtained indicate a positive relationship between dose and BNMN frequency as calculated by the linear regression coefficient, showing significant increases in the frequency of MN and BNMN (binucleated cells with MN) in the subgroup of patients that received more than 500 MBq. Taking into account that the patients studied were treated with relatively low doses of 131I, our positive results support the view that the MN assay is sensitive enough to monitor the chromosome damage resulting from the exposure.

Administration, Oral↗
PubMed1997

Genotoxicity of humic acid in cultured human lymphocytes and its interaction with the herbicides alachlor and maleic hydrazide.

The genotoxicity of humic acid and its possible interaction with the herbicides alachlor and maleic hydrazide have been evaluated in cultured human lymphocytes from two donors. Humic acid and the two herbicides have been tested (alone and combined) for sister-chromatid exchange (SCE) induction. In addition, the effect of two different preincubation times, 2 and 24 hr, was analyzed. The results indicate that humic acid and the herbicides alachlor and maleic hydrazide appear to significantly enhance the frequency of SCE, the effect of the herbicides being more pronounced. With reference to the possible interaction of humic acid with the herbicides, the results do not show a common pattern, although mainly an additive effect was obtained. Nevertheless, there is some evidence suggesting that antagonism may occur, especially in the combined treatment of humic acid and maleic hydrazide.

Acetamides↗
PubMed1997

Decrease in platelet, erythrocyte and lymphocyte acetylcholinesterase activities due to the presence of protease inhibitors in the storage buffer.

The effect of the presence of protease inhibitors in the storage buffer on acetylcholinesterase (AChE) activity was studied in crude membrane preparations from sheep platelets before and after solubilization of the membranes with Triton X-100. Although sensitive to the action of trypsin, the biological activity of AChE remained unchanged for as long as 6 days at 4 degrees C in a protease-inhibitor-free medium. At 10(-5) M final concentration PMSF reduced AChE activity to 50% after 24 hours of storage. This reduction was abolished in mixtures in which PMSF was present together with 3 mM EGTA, 5 mM EDTA and 0.1 mg/mL trypsin inhibitor. Nevertheless, under these conditions, storage periods longer than 24 hours still drastically reduced AChE activity. A mixture of EDTA, EGTA and trypsin inhibitor also produced a decrease in AChE activity after 24 hours. A more complex cocktail of inhibitors including several commonly used peptides decreased AChE activity only if PMSF or EDTA were present in the mixtures. Similar results were obtained with sheep erythrocytes or lymphocytes, and bovine erythrocytes.

Acetylcholinesterase↗
PubMed1997

Aneugenic activity in human cultured lymphocytes. An overall study with colchicine using the micronucleus assay and fluorescence in situ hybridization techniques.

The effects induced by aneugenic agents on chromosome segregation are manifold. The biological relevance of these effects has led to the development of assays specifically detecting aneugens. In this context, the micronucleus (MN) assay in binucleated human lymphocytes along with FISH has been considered a pertinent tool for detecting aneugenic and clastogenic activity. However, the MN assay is insensitive in detecting aneugenic effects other than chromosome loss. By using the aneugenic model compound colchicine and X chromosome centromere-specific FISH, we have shown that besides chromosome loss in binucleated cells, other effects such as MN in mononucleated cells, cells arrested at metaphase, polyploidy and non-disjunction are also consistently induced by aneugenic agents. A chromosome 1 centromeric probe was used simultaneously with X chromosome centromeric labeling in mononucleated cells in order to distinguish polysomy from polyploidy. It is concluded that all these effects should be considered for a comprehensive evaluation of aneugenic activity.

Adult↗