Biomedical subjects

A Creus

Publications and source records attributed to A Creus.

At least 55 records · Page 3Linked to original sources

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

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↗

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

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↗

PubMed1997

Radioactive iodine induces clastogenic and age-dependent aneugenic effects in lymphocytes of thyroid cancer patients as revealed by interphase FISH.

After the Chernobyl nuclear accident, a dramatic 131I-related increase in the incidence of thyroid cancer has been reported in exposed children. However, little is known about the eventual genotoxic effects of 131I in exposed humans. Thyroid cancer patients are usually treated with 131I and, therefore, they provide us with an opportunity to study cytogenetic damage induced by known doses of this radionuclide. FISH techniques have been employed to study the origin of micronuclei as well as X chromosome non-disjunction and X chromosome numerical abnormalities in lymphocytes from 131I-treated women suffering from thyroid cancer. Blood was sampled before and 1 week after 131I treatment. Cells were analysed with either pancentromeric FISH to classify micronuclei or X chromosome centromere-specific FISH in mononucleated and binucleated cells to evaluate X chromosome numerical abnormalities and non-disjunction respectively. Our data indicate that 131I-induced clastogenic and age-dependent aneugenic effects in the lymphocytes of exposed patients. The X chromosome was not preferentially involved in the aneugenic effect induced by 131I. It is concluded that besides its major clastogenic effect, 131I can also induce an X chromosome-independent aneugenic activity mainly in patients with spontaneous proneness to chromosome loss.

Adolescent↗

PubMed1996

Genotoxic evaluation of the herbicide trifluralin on human lymphocytes exposed in vitro.

The herbicide trifluralin 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 for SCE and MN demonstration were also treated with S9 fraction. From our results we can conclude that trifluralin was able to exert a weak cytotoxic effect, reducing both the proliferative rate index (PRI) and the cytokinesis block proliferation index (CBPI), and also to induce a slight but statistically significant increase in the frequency of SCE. Under our conditions of testing, no genotoxic effects of trifluralin were observed in the CA and MN assays.

Cells, Cultured↗

PubMed1996

Sister-chromatid exchanges (SCE) induction by inhibitors of DNA topoisomerases in cultured human lymphocytes.

The induction of sister-chromatid exchanges (SCE) in cultured human lymphocytes by four inhibitors of DNA topoisomerases: m-amsacrine, camptothecin, etoposide and nalidixic acid has been evaluated. Although the four compounds apparently increase the frequency of SCE, the effect of nalidixic acid is weak because only a statistically significant positive response was found in one donor at the highest concentration (500 microM). The other compounds tested act as SCE inducers in both donors, camptothecin being the most effective. In addition, the influence of these four topoisomerase inhibitors on the SCE frequency induced by MMC was also analysed. The results reveal that less than additive SCE effect was induced by the combined treatments which could suggest that the process leading to SCE induction by MMC and the four inhibitors of DNA topoisomerases are not totally independent.

Amsacrine↗

PubMed1996

No increase in micronuclei frequency in cultured blood lymphocytes from a group of filling station attendants.

Service station attendants are workers that are definitely exposed to petroleum derivatives. Taking into account that this exposure has been considered to possess genotoxic risk, here we present data on the biomonitoring of a group of 50 service station workers and 43 controls. Micronuclei (MN) from peripheral blood lymphocytes has been considered as the genetic endpoint to be studied and, in addition, data on the concentration of aromatic hydrocarbons at the workplace, urinary metabolites and differential white blood cell count have also been analysed. The results obtained indicate no significant differences between petrol station attendants and controls, when the effects of petrol exposure were investigated by differential white blood cell count and analysis of MN frequencies in phytohaemagglutinin-stimulated lymphocytes. Regarding the urinary metabolites, a significant increase in the phenol level was found in the exposed workers.

Adolescent↗

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↗

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

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↗