Biomedical subjects

R Marcos

Publications and source records attributed to R Marcos.

At least 91 records · Page 5Linked to original sources

PubMed1996

Chromosomal aberration analysis in 85 control individuals.

Chromosomal aberrations (CA) were studied in the peripheral blood lymphocytes of 85 healthy male volunteers from Barcelona (Catalonia, Spain). The effect that factors such as age, life style, work exposure and medical treatment had on the cytological endpoints was studied by means of a Poisson regression model. The results obtained indicate a significant positive relationship between the age of the subjects analyzed and the total of chromosome-type aberrations. With respect to the other variables analyzed, a positive association was found between the frequent consumption of analgesics and the incidence of chromatid-type aberrations.

Adult↗

PubMed1996

Genotoxicity of the herbicides alachlor and maleic hydrazide in cultured human lymphocytes.

The herbicides alachlor and maleic hydrazide were evaluated for genotoxicity in peripheral blood human lymphocyte cultures. Sister-chromatid exchanges (SCE), chromosome aberrations (CA) and micronuclei (MN) were scored as genetic endpoints. To detect possible metabolic modifications in the genotoxicity of both herbicides, the cultures for SCE and MN demonstration were also treated with S9 fraction. From our results we conclude that, in the absence of metabolic activation, the two herbicides induce significant increases in the frequency of SCE, although the concentrations needed to be effective are very different. Thus, alachlor gave positive results at concentrations ranging from 1 microg/ml, and maleic hydrazide at concentrations ranging from 100 microg/ml. In addition, alachlor appears to be clastogenic in both the CA and MN assays, but only at the highest concentration tested (20 microg/ml). The co-treatment with the S9 fraction produced a slight decrease in the induction of SCE with both herbicides: nevertheless, it does not seem to affect the response in the MN assay.

Acetamides↗

PubMed1996

Molecular study of the germinal reversions induced at the white-ivory locus in Drosophila melanogaster.

The white-ivory somatic mutation test of Drosophila melanogaster is based on the reversion of the X-linked eye colour recessive mutation white-ivory to wild-type. Although the exact mechanism of white-ivory reversion is not quite understood, it has been suggested that such reversion, both in somatic and germ-line cells, could be due to the precise excision of the tandemly duplicated 2.96 kb DNA fragment characteristic of the white-ivory mutation. We have attempted to confirm this hypothesis analysing, at the molecular level, different germinal revertants induced by chemical treatment with three well known alkylating agents: ethyl methanesulphonate, methyl methanesulphonate and N-nitroso-N-ethylurea. The molecular analysis of these germ-line revertants, using Southern blot hybridization and polymerase chain reaction techniques, shows that such reversions are associated with the deletion of the 2.96 kb tandemly duplicated DNA sequence of the white-ivory locus.

Alkylating Agents↗

PubMed1996

Termination of disease-modifying drugs in psoriatic arthritis: study of 109 courses of treatment.

Our aim is to study the termination of disease-modifying anti-rheumatic drugs (DMARDs) in psoriatic arthritis (PsA) and the causes of withdrawal. We have reviewed the prospective protocols of patients with PsA and collected the data on treatments and causes of withdrawal. Fifty-four out of 96 patients (48 male and 48 female) have undergone one or more courses of DMARD (n = 109). The life-table analysis shows a survival rate of 6 months for gold sodium thiomalate (GOLD) and sulphasalazine (SSZ), and 16 months for methotrexate (MTX). The Mantel-Haenszel test finds statistical differences between GOLD and MTX. There are no differences between MTX and SSZ or between GOLD and SSZ. The absence of differences for MTX and SSZ could be explained by the heterogeneity of both groups. The most common cause of withdrawal for GOLD and SSZ are adverse effects.

Antirheumatic Agents↗

PubMed1996

Cytogenetic analysis in peripheral lymphocytes of cancer patients treated with cytostatic drugs: results from an EC Collaborative Study.

Many of the cytostatic drugs commonly used in cancer chemotherapy treatments have been shown to be genotoxic in vivo and in vitro. We present a cytogenetic collaborative study on 13 cancer patients treated with different antitumor agents. For comparison we also carried out a cytogenetic analysis on 14 healthy untreated controls. The frequency of sister chromatid exchanges and structural chromosome aberrations in peripheral blood lymphocytes of the cancer patients was determined prior to the treatment, just after it and 3-7 weeks later. The results obtained show clear differences between the basal levels of cytogenetic alterations in cancer patients, even though the mean value is higher in this group than the basal levels of the group of healthy individuals. Treatment with cytostatics increases the frequency of both cytogenetic biomarkers analyzed, which declined to values similar to those initially observed several weeks after the treatment. Our data are in qualitative and quantitative agreement with other results previously found by other authors.

Adult↗

PubMed1996

[Neonatal convulsions in health care. II. Prognostic factors].

OBJECTIVE: To determine whether neonatal convulsions make up a homogeneous pathological group when it comes to establishing indices of prognosis. DESIGN: Descriptive study of retrospective cohorts. SCOPE: Twenty five cases of neonatal convulsions out of the 12,427 new born babies in the province of Albacete in the period 1991-1993 and the follow-up of their development up to December 1994. MATERIAL AND METHODS: Univariant analysis (variable dependent evolution; variable independent: type of crisis identified, interictal clinical features, EEG pattern and cerebral Eco-CT/MR) and multivariant analysis using a maximal logistic regression model. RESULTS: I. Univariant analysis. Type of crisis: we found differences between the types of crises presented (clonic, focal tonic, myoclonic, subtile with apnea, with no obvious crisis) and the prognosis, but no significant result. Neurological findings between crises: the RN who showed no change in consciousness following the convulsion had a better prognosis than those with changes in the level of consciousness between crises. The difference was significant (P = 0.03). Post-critic EEG pattern. The RN with a normal or a focal EEG were grouped together as opposed to those who showed alterations which were multifocal, had changes in the basic rhythm, were paroxysmal or of low voltage; the first type of EEG indicated the best prognosis (OR = 12.0; IC 95%; 1.1-159.5; p = 0.2). Radiodiagnosis: the RN with no changes on Eco or CT-RM had better prognoses (p > 0.001) than those with pathological ones. None had pathological sequelae (OR = 0.0). II. Multivariant analysis. The final method only retained the variable Rx (Radiodiagnosis) which implied that the other variables lost significance when corrected for association with Rx (p < 0.001) OR = 0.0. DISCUSSION: Although the clinical and EEG findings are indicators of prognosis, they lose their significance when correction is made for the underlying cerebral damage. The cause of the convulsions and the associated underlying cerebral lesion is the most important factor in determining the final outcome.

Electroencephalography↗

PubMed1995

A cytogenetic follow-up study of thyroid cancer patients treated with 131I.

To determine the genotoxic risk associated with therapeutic exposure to 131I, we studied the presence of micronuclei (MN) in binucleated peripheral blood lymphocytes of a group of 22 women, patients of thyroid cancer, who received 131I sodium iodide orally as an adjuvant after total thyroidectomy. The cytogenetic study was conducted following annual check-up, the patients having received the therapeutic dose between 1 and 5 years before the study. The results show that there are no significant differences in MN frequency between the patients and the control group, the latter composed of 19 unexposed women. These findings could indicate that any possible genetic damage induced by therapeutic exposure to 131I is eliminated after a period of 1 year.

Adult↗

PubMed1995

Genotoxic evaluation of ten carcinogens in the Drosophila melanogaster wing spot test.

To provide further background data on the wing spot somatic mutation and recombination assay, 10 selected carcinogens (acetamide, acrylamide, benzo(a)pyrene, cyclophosphamide, diethylstilbestrol, 4-nitroquinoline N-oxide, propyleneimine, safrole, thiourea, and o-toluidine) were tested in this assay. 72-h-old third-instar larvae, trans-heterozygous for 2 recessive wing cell markers: multiple wing hairs (mwh) and flare3 (flr3) were fed with 3 concentrations of each carcinogen during the rest of their development until pupation, and the genotoxic effects were measured as significant increases in the appearance of visible mutant hair clones on the adult wing blade. Our results show that 6 of the carcinogens tested produce significant increases in wing spot frequency, at least at one of the concentrations assayed. Benzo(a)pyrene, diethylstilbestrol, safrole and thiourea were the compounds that did not increase the incidence of mutant clones.

4-Nitroquinoline-1-oxide↗

PubMed1995

Somatic reversion of some copia-like induced mutations, at the white locus of Drosophila melanogaster, after treatment with alkylating agents.

It has been suggested that transposable elements can be associated with different types of genotoxic effects. For this reason it seems appropriate to outline suitable systems to detect changes in the phenotypic expression of the loci containing transposable elements, as well as those agents that induce such changes. The sex-linked white locus offers a suitable experimental system for studying such events because most of the spontaneous mutations at the white locus are the result of insertions of repeated mobile sequences, and it is easy to follow mutational changes of the locus due to the possibility of detecting even slight changes in eye color. Here we report the results obtained in different strains of Drosophila melanogaster with copia-like induced mutations at the white locus, after treatment with three alkylating agents: ethyl methanesulfonate (EMS), methyl methanesulfonate (MMS), and N-nitroso-N-ethylurea (ENU). The three insertional white mutants used in this work were wa4, wbf, and wsp55, with the wa2 mutation used as control because its mutant phenotype is the result of a point mutation instead of the insertion of a DNA fragment. Our data constitute evidence that EMS, MMS, and ENU induce a clear increase in the frequencies of somatic-revertant sectors in the three strains carrying a white allele with an inserted copia-like element. For the wa2 strain, whose mutant phenotype is the result of a point mutation, only ENU at the highest concentration tested is able to induce a significant increase in the somatic reversion frequency. In addition, our results indicate that the use of D. melanogaster strains with transposable elements in the white locus is suitable for detecting genotoxic damage induced by chemicals.

Alkylating Agents↗

PubMed1995

Growth, hormonal status and protein turnover in rats fed on a diet containing peas (Pisum sativum L.) as the source of protein.

The inclusion of peas (Pisum sativum L.) as the source of protein in the diet of growing rats brings about a reduction in growth rate as well as the impairment in the liver, muscle and spleen weights as compared with casein fed controls. Also, a fall in plasma glucose, triglycerides and protein was observed in the legume fed animals, while no changes in cholesterol levels were found. Furthermore, the rats fed on the diet containing peas showed lower levels of plasma insulin, corticosterone, IGF-I and T4 as compared with casein controls. Liver and muscle total protein (mg) and total DNA (mg) were markedly decreased in the legume fed animals, but DNA/g, protein/DNA and RNA/protein ratios were similar in both dietary groups. Likewise, liver and muscle fractional synthesis rates were similar in the casein and legume groups, while the whole body protein synthesis is assumed to be lower in the legume fed animals due to differences in body weights. It is concluded that animals fed on a diet containing peas (Pisum sativum L.) as the only source of protein showed less adverse effects than those found with other legumes such as Vicia faba L. or Phaseolus vulgaris L., in which protein quality, antinutritional factors and nutrient availability could be involved.

Animals↗

PubMed1995

SCE analysis in human lymphocytes of a Spanish control population.

SCE (sister-chromatid exchanges), HFC (high frequency cells) and PRI (proliferative rate index) were studied in the peripheral blood lymphocytes of 154 healthy male volunteers, from Barcelona (Spain). SCE, HFC and PRI variability between and/or within individuals was estimated by means of a mixed linear model. This model allows a determination of the relationship between confounding factors (demographics, life style, work exposure and medical history) and the cytogenetic and cytokinetic parameters analyzed. The results obtained indicate the existence of an important intra-individual heterogeneity in SCE rates, as well as in HFC and PRI values. Although age did not seem to affect either the SCE frequency or the HFC percentage, it showed a significant positive association with the presence of cells with higher SCE frequencies. With respect to the confounding factors, only cigarette smoking increased the SCE rates and the HFC values. On the other hand, PRI mean showed significant differences dependent on age and was inversely correlated with alcohol consumption and X-ray exposure.

Adult↗

PubMed1995

Temporary variations in chromosomal aberrations in a group of agricultural workers exposed to pesticides.

The induction of chromosomal aberrations (CA) was studied in the peripheral lymphocytes of 29 male agricultural workers occupationally exposed to several pesticides. To investigate possible exposure-related changes in the frequency of CA, a longitudinal study has been conducted. Two blood samples were taken from each individual: one in a period of high exposure (spring-summer) and the other in a period of lower exposure (autumn-winter). Simultaneously, two matched control groups constituted by 29 and 24 healthy men, without indication of exposure to pesticides, were analysed. During the period of major exposure, the group of agricultural workers showed a significant increase in the frequency of CA, mainly of chromatid-type, when compared to the unexposed control group; nevertheless, this increase in the expression of CA was not found in the period of minor exposure. This finding could indicate that the frequency of CA is related to the intensity of the pesticide exposure, and that CA have a relatively short-life, recovering the control value a few months later. In addition to the cytogenetic analysis, biochemical and haemotological blood parameters were also analysed and no significant variations were detected.

Agriculture↗

PubMed1995

Genotoxicity testing of five compounds in three Drosophila short-term somatic assays.

To provide further background data for the somatic mutation and/or recombination tests in Drosophila melanogaster, we have evaluated the response in 3 assays (zeste-white, white-ivory and wing spot) of 5 chemicals classified by the U.S. National Toxicology Program (NTP) as genotoxic non-carcinogens (or ambiguous). The selected compounds were 2-chloromethylpyridine, 1-nitronaphthalene, 4-nitro-o-phenylenediamine, 3-nitropropionic acid and p-phenylenediamine. Our results show that all the compounds tested produce significant increases in the frequency of mutant clones, in at least one of the assays, p-phenylenediamine being the compound which presents a clearer mutagenic activity, and the wing spot test, the assay that detects more genotoxic compounds (4/5).

Animals↗

PubMed1995

Induction of micronuclei by five pyrethroid insecticides in whole-blood and isolated human lymphocyte cultures.

Five pyrethroid insecticides: cypermethrin, deltamethrin, fenpropathrin, fenvalerate and permethrin, were tested for their ability to induce micronuclei in both whole-blood (WB; three donors) and isolated human lymphocyte (IL, 2 donors) cultures, by using the cytokinesis-block method with 6 micrograms/ml cytochalasin B (Cyt-B). Fenvalerate and permethrin were tested with two different concentrations of Cyt-B (3 and 6 micrograms/ml). At the concentration ranges tested, all the five pyrethroids induced clear dose dependent cytotoxic effects, fenpropathrin being the most toxic. Nuclear division index (NDI) and the newly introduced index of cytotoxicity, the cytokinesis block proliferation index (CBPI), reflected the dose dependency more accurately than the percentage of binucleated cells did. CBPI is similar to NDI except that it estimates the average number of cell divisions that the cell population has gone through, and, therefore, classifies both trinucleate and tetranucleate cells into the same category. Cypermethrin and fenpropathrin slightly increased the number of MN and micronucleated cells in WB lymphocyte cultures from two out of the three donors. Deltamethrin produced a positive response only in WB cultures of one donor and in IL cultures of another donor. Permethrin gave mostly negative results, although it increased the MN frequency in WB cultures of one donor when 6 micrograms/ml Cyt-B was used. Fenvalerate did not significantly induce MN. With certain reservations to the purity and isomer composition of each pesticide, the existing information appears to support the idea that pyrethroid insecticides have a weak (cypermethrin, deltamethrin and fenpropathrin) or nule (fenvalerate and permethrin) genotoxic activity in vitro.

Adult↗

PubMed1995

Herbicide-induced DNA damage in human lymphocytes evaluated by the single-cell gel electrophoresis (SCGE) assay.

The genotoxicity of the herbicides, alachlor, atrazine, maleic hydrazide, paraquat and trifluralin has been evaluated in the single-cell gel electrophoresis (SCGE) assay by using human peripheral blood lymphocytes. All treatments were conducted with and without the presence of an external bioactivation source (S9 mix). The results indicate that all the herbicides tested are able to give positive results by increasing the comet tail length, which would confirm both the genotoxicity of the herbicides and the sensitivity of the assay in front of these chemicals. Alachlor and atrazine give similar results in treatments with and without S9, while when the S9 mix was not used paraquat and trifluralin genotoxicity was higher. On the other hand, although maleic hydrazide genotoxicity was higher when S9 mix was used at normal pH (7.4), our data show that its genotoxicity depends largely on the pH solution, increasing as the pH decreased.

Biotransformation↗

PubMed1995

The suitability of the micronucleus assay in human lymphocytes as a new biomarker of excision repair.

The cytokinesis blocked micronucleus assay is relatively insensitive to detect agents that predominantly induce excision repairable DNA lesions. However, it has been recently proposed that excision-repairable DNA lesions induced in G0/G1 phase can be converted to micronuclei by using inhibitors of the gap filling step of excision repair so that unfilled gaps are converted to double stranded breaks after S phase and micronuclei (MN) at completion of mitosis. As it has been recently demonstrated this process could be improved by combining cytosine arabinoside (ARA-C) and hydroxyurea (HU). In the present work, we have investigated the suitability of this new approach by studying its ability to detect excision repairable DNA lesions induced by 10 pesticides (alachlor, atrazine, cypermethrin, deltamethrin, fenpropathrin, fenvalerate, maleic hydrazide, paraquat, permethrin and trifluralin) and 3 well-known mutagenic agents (ethyl methane sulphonate, EMS; methylnitrosourea, MNU; and mytomicin C, MMC). Our results showed that the combination of ARA-C and HU substantially increased the level of MN in whole blood lymphocyte cultures, but it provided an excess of toxicity when further treatments, such as MNU, were performed. When ARA-C alone was used, the ARA/CBMN assay appeared to be highly sensitive and specific in detecting agents known to induce excision repairable DNA lesions. Thus, EMS and MNU but not MMC greatly induced DNA excision repair. On the other hand, alachlor, permethrin and, to a lesser extent, trifluralin and fenpropathrin also increased the ratio of excision repairable DNA lesions converted to MN. On the contrary, atrazine, cypermethrin, deltamethrin, fenvalerate, maleic hydrazide and paraquat did not induce excision repair.

Adult↗

PubMed1995

Micronuclei induced by alachlor, mitomycin-C and vinblastine in human lymphocytes: presence of centromeres and kinetochores and influence of staining technique.

Antikinetochore antibodies and fluorescence in situ hybridization with an alphoid centromeric probe were applied to the cytokinesis-block micronucleus (MN) assay to study the suitability of these methodologies to detect clastogenic/aneugenic activity in isolated human lymphocytes. The chemicals selected for this study were the herbicide alachlor, the clastogen mitomycin-C (MMC), and the aneugen vinblastine sulphate (VBL). Furthermore, MN frequencies obtained from slides stained with May-Grünwald-Giemsa (MGG) and with the DNA fluorochrome 4',6'-diamidino-2-phenylindole (DAPI) were compared to check if the DNA-specific DAPI facilitated a more accurate recording of MN than the unspecific MGG. The results showed that the detection of kinetochores (KC) or centromeres (CM) within MN are equally reliable and sensitive techniques to study the mode of action of clastogenic and aneugenic agents. The comparison of CM and KC detection in control cultures suggested that up to 17% of spontaneous chromosome-containing MN may be due to KC disruption, whereas the majority are caused by dysfunction in other components of the mitotic apparatus. Alachlor (7.5-20 micrograms/ml) and MMC (0.6 microM) acted as pure clastogens without aneugenic activity, inducing exclusively KC- and CM-negative MN. VBL produced primarily KC- and CM-positive MN, in accordance with its known mechanism of action. A comparison between CM and KC data in the VBL treatment suggested that some 7% of KC-containing MN may not be detected by the probe. The frequencies of MN were generally higher in slides stained with DAPI than in those stained with MGG, especially in controls and clastogen-treated cultures.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetamides↗

PubMed1994

Further studies with the somatic white-ivory system of Drosophila melanogaster: genotoxicity testing of ten carcinogens.

To provide further background data for the white-ivory somatic mutation Drosophila assay, ten selected carcinogens (acetamide, acrylamide, benzo(alpha)pyrene, cyclophosphamide, diethylstilbestrol, 4-nitroquinoline N-oxide, propyleneimine, safrole, thiourea, and o-toluidine) have been tested in this system. Seventy-two hours after egg laying, larvae were fed with different concentrations of each carcinogen during the rest of their development until pupation, and the genotoxic effects were measured as significant increases in the appearance of visible mutant clones of ommatidia in the eyes of the emerging adult flies. Our results indicate that three of the ten carcinogens tested (cyclophosphamide, 4-nitroquinoline N-oxide, and propyleneimine) were strong genotoxic agents, two (diethylstilbestrol and acrylamide) induced significant positive results but without a dose-response relationship, and safrole was weakly positive. On the other hand, acetamide, benzo(alpha)pyrene, thiourea, and o-toluidine were unable to increase the frequency of mutant clones.

Animals↗