Biomedical subjects

G Ribas

Publications and source records attributed to G Ribas.

16 recordsLinked to original sources

PubMed2006

Estrogen and progesterone receptor gene polymorphisms and sporadic breast cancer risk: a Spanish case-control study.

Estrogens, and to a lesser extent progesterones, influence the proliferation, differentiation and physiology of breast tissue as well as the development and progression of breast cancer. Genetic variants in the steroid hormone receptor genes ESR1 and PGR (belonging to the nuclear receptor superfamily) could therefore modify sporadic breast cancer susceptibility. Two studies have shown a protective effect associated with variants in ESR1 in 2 distinct populations. We studied 4 single nucleotide polymorphisms (SNPs) in ESR1 and 4 in PGR in 550 consecutive and unrelated sporadic Spanish breast cancer patients and 564 healthy Spanish controls. We observed a dominant protective effect for the S10S variant in ESR1, with an estimated odds ratio (OR) of 0.75 (95% CI = 0.58-0.97; p = 0.03) although functional studies did not show changes in the RNA stability. A small subset of individuals carried a haplotype combination that corroborates this protection. No other SNP considered in either gene was found to be associated with sporadic breast cancer. Our results obtained in a European population confirm the protective role of the S10S variant in ESR1, previously reported in an Asian and a European-American population.

Adult↗

PubMed2006

FANCD2 associated with sporadic breast cancer risk.

Several components of the Fanconi anaemia (FA) family of proteins allow the formation of the DNA repair complex foci formed by proteins such as BRCA1/2 and RAD51. Because the genes that participate in the DNA repair pathway have been described as low-penetrance breast cancer susceptibility genes, we postulated that variants in FA genes could also be associated with sporadic breast cancer risk. We studied seven SNPs in FANCA, FANCL and FANCD2 in a total of 897 consecutive and non-related sporadic breast cancer cases and 1033 unaffected controls from the Spanish population. We observed a statistically significant association with sporadic breast cancer for the variant rs2272125 (L1366L) located on FANCD2 (OR per allele=1.35; 95% C.I. 1.09-1.67; P=0.005). Both haplotype and diplotype analyses confirmed this association, where one haplotype and pooled diplotypes carrying it were associated with more than 4-fold risk (P=0.007 and P=0.006, respectively). Screening for potential causal variants in FANCD2 was performed, detecting one in the putative promoter region, which is located in a phylogenetically conserved motif with consensus binding sites for some transcriptional factors, suggesting a functional implication. Our data indicate that a relationship between FANCD2 and sporadic breast cancer risk may exist.

Adult↗

PubMed2003

Complex haplotypic structure of the central MHC region flanking TNF in a West African population.

TNF polymorphisms have been associated with susceptibility to malaria and other infectious and inflammatory conditions. We investigated a sample of 150 West African chromosomes to determine linkage disequilibrium (LD) between 25 SNP markers located in an 80 kb segment of the MHC Class III region encompassing TNF and eight neighbouring genes. We observed 45 haplotypes, and 22 of them comprise 80% of the sample. The pattern of LD is remarkably patchy, such that many markers show no LD with adjacent markers but high LD with markers that are much further away. We introduce a method of examining the implications of LD data for disease association studies based on sample size considerations: this shows that certain TNF polymorphisms would be likely to yield positive associations if the true disease allele resided in LTA or BAT1. We conclude that detailed marker maps are needed to resolve the causal origin of disease associations observed at the TNF locus.

Adult↗

PubMed2001

Single-nucleotide polymorphism detection by denaturing high-performance liquid chromatography and direct sequencing in genes in the MHC class III region encoding novel cell surface molecules.

The class III region of the human major histocompatibility complex (MHC) contains approximately 59 genes, many of which encode polypeptides with a variety of different functions. Eight of these genes are of particular interest because they encode novel surface molecules that could be involved in immune and/or inflammatory responses and are excellent candidates as disease susceptibility loci. These molecules are members of two different superfamilies, the immunoglobulin superfamily (1C7, G6B, and G6F genes) and the leucocyte antigen-6 superfamily (G6C, G6D, G6E, G5C, and G5B genes). Some level of variation was found when overlapping genomic DNAs from different haplotypes were compared. The present work describes a systematic search for single-nucleotide polymorphisms (SNPs) in these genes using direct sequencing and denaturing high-performance liquid chromatography (DHPLC) in 24 unrelated healthy individuals. We validated the DHPLC methodology by first studying the 1C7 gene. This gene was directly sequenced in all 24 samples, and DHPLC was found to resolve all the polymorphic sites present in the heterozygote samples tested. We screened the rest of the genes by DHPLC only, and only those chromatograms that revealed a polymorphic profile were sequenced. We detected one SNP every 489 bp in the 18 kb of DNA studied, corresponding to theta = 4.61x10-4. The diversity in noncoding regions is 1 SNP/560 bp, but a higher frequency was detected in coding regions with 1 SNP/423 bp corresponding to theta =5.33x10-4. Of the coding SNPs, 63.6% caused amino acid substitutions. The power of this study is emphasized by the fact that of the 37 SNPs/indels detected, only 6 can be found in the SNP database at the NCBI.

Antigens, Ly↗

PubMed1999

Genes encoding three new members of the leukocyte antigen 6 superfamily and a novel member of Ig superfamily, together with genes encoding the regulatory nuclear chloride ion channel protein (hRNCC) and an N omega-N omega-dimethylarginine dimethylaminohydrolase homologue, are found in a 30-kb segment of the MHC class III region.

Many of the genes in the class III region of the human MHC encode proteins involved in the immune and inflammatory responses. We have sequenced a 30-kb segment of the MHC class III region lying between the heat shock protein 70 and TNF genes as part of a program aimed at identifying genes that could be involved in autoimmune disease susceptibility. The sequence analysis has revealed the localization of seven genes, whose precise position and order is cen-G7-G6-G6A-G6B-G6C-G6D-G6E-tel, five of which are fully encoded in the sequence, allowing their genomic structures to be defined. Three of them (G6C, G6D, and G6E) encode putative proteins that belong to the Ly-6 superfamily, known to be GPI-anchored proteins attached to the cell surface. Members of the family are specifically expressed and are important in leukocyte maturation. A fourth gene, G6B, encodes a novel member of the Ig superfamily containing a single Ig V-like domain and a cytoplasmic tail with several signal transduction features. The G6 gene encodes a regulatory nuclear chloride ion channel protein, while the G6A gene encodes a putative homologue of the enzyme N omega,N omega-dimethylarginine dimethylaminohydrolase, which is thought to be involved in regulating nitric oxide synthesis. In addition, three microsatellite markers, 9N-1, 82-2, and D6S273 are contained within the sequence, the last two of which have been reported to be strongly associated with the autoimmune disease ankylosing spondylitis.

Amidohydrolases↗

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↗

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

Effects in the Comet assay of storage conditions on human blood.

The Comet assay is a rapid and sensitive method for analyzing single cells for DNA damage. Using human lymphocytes, the assay is particularly useful for human monitoring studies, as well as for in vitro genotoxicity testing of chemicals. In such studies, it is not always possible to collect and process matched samples on the same day as the blood is taken. It would be useful if some samples could be stored and examined at a different time, without loss of viability or other factors affecting responses. It is thus important to understand the effects of storage conditions on blood to be used in such studies and how exposure or treatment might modify such responses. In a joint study in two laboratories, blood was taken from various donors and stored under different conditions. It was examined on day 1 (day on which sample was taken) and days 2, 3, 4, 5, or 8 at room temperature, 4 degrees C, or -20 degrees C. Cells were treated after storage (from day 2 onward) with bleomycin (BLM) and ethylnitrosourea (ENU). The data were analyzed either by eye (classifying cells with different categories of damage) or by using a computerized image analysis system (Kinetic Imaging Ltd., Liverpool UK. Software Package Comet 3.0) where the tail moment, which is considered to be a sensitive measurement, has been analyzed. There was no loss of cell viability at 4 degrees C or room temperature up to 8 days when measured by trypan blue dye exclusion. Findings suggest that on days 1-4 for the untreated samples at room temperature or 4 degrees C there were no biologically meaningful changes in both the different categories of cell damage and tail moment data. In treated cultures up to day 4, either at room temperature or at 4 degrees C, responses were only minimally affected and changes were considered not to be of biological significance. However, there was slightly less variability between samples at 4 degrees C than at room temperature in one laboratory. The reverse was true in the other. This would suggest that samples can probably be stored up to day 4 at 4 degrees C or room temperature without any untoward effects. Provided samples can be processed within this 4-day time frame, it would not seem necessary to cryopreserve samples at -196 degrees C.

Bleomycin↗

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

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↗

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↗

PubMed1994

Genotoxicity of tritiated water in human lymphocytes.

The present study was carried out to evaluate the genotoxicity of tritium, administered as tritiated water, in peripheral blood human lymphocyte cultures. Sister-chromatid exchanges (SCE) and chromosome aberrations (CA) were scored as genetic endpoints. From our results we can conclude that beta-radiation from low concentrations of tritium was able to induce a significant increase in the frequency of CA, although it was ineffective in increasing the frequency of SCE.

Beta Particles↗

PubMed1992

Genotoxicity of four herbicides in the Drosophila wing spot test.

The herbicides alachlor, atrazine, maleic hydrazide and paraquat were evaluated for genotoxicity in the Drosophila melanogaster wing spot test. Third-instar larvae trans-heterozygous for two recessive mutations of wing trichomes, multiple wing hairs (mwh) and flare (flr3), were treated by chronic feeding with different concentrations of the four herbicides. Feeding ended with pupation of the surviving larvae. The genotoxic effects were determined from the appearance of clones of cells with mwh, flr3 or mwh-flr3 phenotypes. Exposure to maleic hydrazide resulted in a significant increase in the frequency of the three categories of spots recorded (small single, large single and twin spots) in a dose-related fashion. Exposure to alachlor induced significant increases in both small and total spots at the four concentrations assayed and in the frequency of twin spots at the highest concentration tested (10 mM). Atrazine and paraquat also induced significant increases in both small and total spots at three of the four concentrations tested, without indication of a direct dose-effect relationship.

Acetamides↗

PubMed1992

Germinal and somatic mutation induction in Drosophila after treatment of larvae with tritiated water.

The present study was carried out to evaluate the mutagenicity of tritium, administered as tritiated water, in Drosophila melanogaster. Larvae were fed on tritium-treated medium during their development. Germinal and somatic mutation induction was detected by means of the sex-linked recessive lethal and the wing spot tests, respectively. Our results show that beta-radiation from tritium is able to induce significant increases in the frequency of both germinal and somatic mutations.

Animals↗

PubMedDate not supplied

Genotoxic evaluation of the herbicide paraquat in cultured human lymphocytes.

The widely used herbicide paraquat was evaluated for genotoxicity in peripheral blood human lymphocyte cultures. Sister-chromatid exchanges (SCE), chromosome aberrations (CA), and micronuclei (MN) were scored as genetic endpoints. Paraquat was administered either alone or in combination with an external source of metabolic activation. Our data indicate that paraquat induced slight but significant increases in the frequency of SCE. This genotoxic effect was not modified by cotreatments with S9 fraction from rat liver. However, paraquat did not increase the frequency of CA and MN, indicating that this bipyridylium compound is not effective in these assays, which would mean a general lack of effectiveness of the herbicide to induce clastogenic damage. In addition, cotreatments with the S9 fraction, did not modify the genotoxic ability detected in the SCE assay.

Animals↗