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F N Dulout

Publications and source records attributed to F N Dulout.

At least 37 records · Page 2Linked to original sources
PubMed2001

[Activation of K-ras and c-erbB-2 protooncogenes in human colonic adenocarcinomas].

Although data on genetic alterations leading to development of colorectal cancer are abundant, no specific genetic alteration has been demonstrated for each class of tumor. The colorectal cancer phenotype is originated from an accumulation of different genetic alterations. The nature of these alterations, their order of appearance, and their associations vary greatly from one tumor to another, suggesting that the concept of a unique model of carcinogenesis is not applicable to these tumors. The aim of the present work was to study the association between K-ras and c-erbB-2 mutations and different clinicopathological variables in fifty-four samples from adenocarcinomas of the colon. The detection of K-ras activation was performed by specific enriched PCR. The genomic differential polymerase chain reaction with the single copy reference gene was employed for the detection of c-erbB-2 gene amplification. K-ras mutations were detected in 16 cases (29.63%) and c-erbB-2 amplifications in 1 sample (1.85%). Statistical analysis showed a significant association between K-ras codon 12 mutation frequency and Duke's stage B (p < 0.05). On the other hand, there was no association in relation to the other studied parameters. These results could indicate the occurrence of K-ras activation in early stages of the disease.

Adenocarcinoma↗
PubMed2001

Micronucleus test in fish from a pampasic pond (Argentina): an estimation of the presence of genotoxic compounds.

The Los Padres pond is one of the commonly shallow, polymictic lakes from the so-called depressed Pampa (Argentina). Its watershed includes one affluent, named Los Padres creek, which flows through horticultural lands wherein great amounts of pesticides are applied. Opposite to this stream, the pond drains into La Tapera creek that is the effluent running toward the sea. Many studies have confirmed the capacity of various pesticides to induce genetic damage. The use of micronucleus (MN) tests in fish has enabled us to detect the presence of contaminants in the lakewater and to evaluate theirgenotoxic effects. For this purpose, water samples were collected during April, August, and December 1999 from both creeks characterized by different environmental conditions. In the laboratory, specimens oftetras Cheirodon interruptus (Pisces, Characidae) were reared in water samples from the two creeks. Control fish were kept in drinking water. Fifteen individuals from each experimental group were sacrificed after 24-, 48-, and 72-hour exposure intervals. Micronucleus frequency in fish erythrocytes was determined, and the Kruskal-Wallis test for statistic analysis was used. We made the following observations: (1) Highly significant differences occurred in MN frequency between the control group and the samples from both creeks. (2) An increase in MN frequency was evident in specimens sampled from the affluent input during the month of December. These results allowed us to conclude that the increase in MN frequency observed in fish belonging to both sampling sites would indicate the existence of genotoxic compounds in the Los Padres pond. The high MN frequency in fish collected near Los Padres creek inlet might be related to the polluted load transported by the affluent and discharged into the lake's surface waters. Future work would allow us to develop efficient methods for predicting the presence of genotoxic contaminants. It would be possible then to propose strategies for regulating and decreasing the sources of pollution that affect human health.

Animals↗
PubMed2000

Aneugenic effects of some metal compounds assessed by chromosome counting in MRC-5 human cells.

Development of a comprehensive test battery is necesary for the evaluation and detection of aneugenic chemicals. The chromosome couting method was used in the present study. The aneugenic ability of cadmium choride (1.0, 2.0 and 4.0x10(-3) mM), cadmium sulfate (3. 3, 6.7x10(-5) and 1.3x10(-4) mM), potassium dichromate (2.5, 5. 0x10(-4) and 1.0x10(-3) mM) and cacodilic acid (1.25, 2.5 and 5. 0x10(-2) mM) were analysed using MRC-5 cells which have a modal diploid number of 2 n=46 with a spontaneous aneuploid or polyploid cells not higher than 13% and 8%, respectively.All compounds induced significant increments of aneuploid cells in relation to negative controls. The frequency of aneuploid cells increased in all treatments with cadmium chloride. Cadmium sulfate induced significant increments of aneuploid cells with the two higher doses. All the doses of potassium dichromate increased the frequency of aneuploid cells although to a lesser degree than the other compounds. In these cases, differences were in the borderline of statistical significance (p<0.05). Moreover, a low number of cells could be analysed in treatments with the highest dose due to the decrease in the mitotic index. Results obtained are coincident with previous reports using the same methodology in the sense that induced aneuploidy was mainly evidenced by the increase of hypodiploid but not hyperdiploid cells. In addition, anaphase-telophase analysis of the effects of the same doses of these metal compounds in CHO cells showed significant increments of lagging chromosomes and increased frequencies of kinetochore positive micronuclei in MRC-5 cells. These findings could be considered as an indication that the main cause of unequal chromosome separation is the failure of kinetochores to attach the spindle apparatus either by alteration of its protein components or by the altered chromatid separation in anaphase.

Aneuploidy↗
PubMed2000

Association between activated K-ras and c-erbB-2 oncogenes with "high-risk" and "low-risk" human papilloma virus types in preinvasive cervical lesions.

Clinical and epidemiological data have linked cervical cancer to the Human Papilloma Virus (HPV) infection. However, the presence of HPV infection alone is not enough to cause tumorigenesis, suggesting a role for additional host-cell genetic factors. The aim of the present work was to study the association of K-ras and c-erbB-2 mutations in cervical tissue samples with different grades of dysplasia and infected with HPV-6 ("low-risk" type) or HPV-16 and HPV-18 ("high-risk" types). Negative HPV-DNA samples were used as controls. The detection of K-ras and c-erbB-2 activation were performed by Artificial Refractory Mutation System (ARMS)-PCR and semiquantitative PCR, respectively. Statistical analysis showed a highly significant difference in K-ras codon 12 mutation frequency between high-risk and low-risk HPV-infected samples (p<0.05). On the other hand, amplification of the c-erbB-2 oncogene appeared associated to tissue samples infected with HPV-6 (p<0.003). Cervical carcinoma appears to arise from a series of well-characterized progressive histological changes, but the genetic alterations necessary for cervical tumorigenesis are not yet clear. These results raise the possibility for a role of certain proto-oncogenes and their activation in cervical neoplasia.

Adult↗
PubMed2000

Clastogenic effect of copper deficiency in cattle.

Copper plays an essential role as a micronutrient. Deficiency of this element (hypocuprosis) in experimental and domestic animals has a severe impact on growth as well as on reproduction. The occurrence of lesions during hypocuprosis is correlated with the depletion of an enzymatic group in which copper takes part. The aim of this work was to analyse chromosomal aberrations in Aberdeen Angus cows of the province of Buenos Aires in relation with the Cu plasma levels. Short term lymphocyte cultures were made from samples obtained from four groups of animals: two groups with normal levels of copper in plasma and two groups with severe hypocupremia. This analysis showed a significant increase of the frequency of chromosomal aberrations (p<0.001) in the hypocupremic groups in relation with control groups. Finally, the Spearman correlation analysis showed a significant negative association (p<0.05) between copper levels and the yield of chromosomal aberrations. The increase of the frequencies of chromosomal aberrations found in the hypocupremic groups could be explained by the higher oxidative stress suffered by these animals. A lower catalytic activity of enzymes such as Cu/Zn superoxide dismutase (Cu/Zn-SOD) and cytochrome-c oxidase could increase the intracellular production of active oxygen species (O(2)(-), H(2)O(2) and OH(o)) with the consequent clastogenic effects.

Animals↗
PubMed2000

Male-mediated introgression of Bos indicus genes into Argentine and Bolivian Creole cattle breeds.

The geographic distribution and frequency of Bos taurus and Bos indicus Y chromosome haplotypes amongst Argentine and Bolivian Creole cattle breeds were studied, using cytogenetic and molecular genetic techniques. A complete correspondence between Y chromosome morphology and the haplotype of the Y-linked microsatellite marker INRA 124 was found in all males examined. The taurine and indicine haplotypes were detected in 85.7 and 14.3% of the males studied, respectively, although these frequencies varied amongst the different breeds examined. The geographic distribution of this polymorphism suggests a pattern of zebu introgression in South America. The highest frequencies of the Zebu Y-chromosome are found in Brazilian populations (43-90%), in the eastern part of the continent, while it is absent in the southernmost breeds from Uruguay and Argentina. Bolivian breeds, at the centre of the continent, exhibit intermediate values (17-41%). This east/west and north/south gradient of male Zebu introgression could be explained by historical events and environmental factors.

Animals↗
PubMed1999

Genotoxic evaluation of the pyrethroid lambda-cyhalothrin using the micronucleus test in erythrocytes of the fish Cheirodon interruptus interruptus.

In order to develop experimental models able to detect genotoxic effects of pollutants in aquatic organisms, the genotoxicity of the pyrethroid lambda-cyhalothrin was studied using the micronucleus test in erythrocytes of Cheirodon interruptus interruptus. The frequency of micronuclei was examined in blood smears obtained from fishes exposed in vivo to three different concentrations (0.05; 0. 01; 0.001 ug/l) of the compound and sacrificed at nine sampling times (24, 48, 72, 96 h and 8, 12, 15, 19 and 23 days). As a positive control fishes were exposed to 5 mg/l of cyclophosphamide. Results obtained demonstrated the genotoxic effects of the pyrethroid in the experimental model employed. The variation in the micronuclei frequencies in the different sampling times could be related to the blood cell kinetics and the erythrocyte replacement. The results could be considered as a validation of the MN test in fishes for the assessment of genotoxic pollutants.

Animals↗
PubMed1999

Differences in K-ras codon 12 mutation frequency between "high-risk" and "low-risk" HPV-infected samples.

OBJECTIVES: The current study was designed to determine the association between K-ras point mutations and the presence of high- and low-risk HPV types in noncancerous samples. METHODS: One hundred fifty-five noncancerous cytological samples from genital specimens positive for HPV-6, -16, or -18 were analyzed for codon 12 ras point mutations. DNA samples were subjected to nested PCR for the detection of HPV genome. Mutations at the first and second bases of K-ras codon 12 were detected using specific enriched PCR. RESULTS: Eleven percent of the HPV-positive samples analyzed showed mutation in K-ras codon 12 (17 of 155). Mutations were detected in 8 of 53 HPV-16- (15%) and 8 of 38 HPV-18-positive samples (21%). Nevertheless, when HPV-6-positive samples were screened for K-ras mutations only 1 of 64 samples was found mutated (1.56%). Statistical analysis using the chi(2) test showed a highly significant difference (chi(2) = 9.865, P < 0.01) when the rate of mutation for samples positive for high-risk HPV types (16 and 18) was compared with the frequency found in low-risk-infected samples (HPV-6). CONCLUSION: These results could be considered an indicator of the association between K-ras codon 12 mutations and the presence of high-risk HPV types.

DNA, Viral↗
PubMed1999

[Analysis of prevalence of point mutations in codon 12 of oncogene K-ras from non-cancerous samples of cervical cytology positive for type 16 or 18 PVH].

Ninety-one non cancerous samples from genital specimens positives for VPH 16 or 18 and 27 non-infected samples as controls were studied. Mutations at codon 12 in K-ras gene was analyzed using enriched alelic PCR technique. Among the samples studied 17.58% showed mutations in this codon. Significant differences were observed between the control group (negative DNA-HPV) and positives DNA-HPV samples (p < 0.01). No differences were found between both viral types in relation to the mutation frequency. The presence of mutations in the K-ras gene in non cancerous cytological samples point out new questions about the role of mutations in proto-oncogenes and the development of cervical cancer.

Cervix Uteri↗
PubMed1997

The effect of butylated hydroxytoluene on the chromosomal damage induced by bleomycin in Chinese hamster ovary cells.

The effect of butylated hydroxytoluene (BHT) on chromosomal damage induced by bleomycin (BLM) in CHO cells was studied. Treatments were performed in cells at quiescent state (90/95% at G0-G1), 2 h after subculture (G1) or 3 h before fixation (G2). Cells were treated for 20 min with BLM plus BHT and subsequently incubated in the presence of BHT until fixation. Results were compared with those obtained from untreated and DMSO-treated controls, from treatments with BLM or BHT alone, from treatments with BLM followed by treatment with DMSO until fixation, and from treatments with BLM plus BHT for 20 min without post-treatment with BHT. BLM induced chromatid- and chromosome-type aberrations in cells treated at G0/G1 or G1 and chromatid-type aberrations in cells treated at the G2 stage. Post-treatment with BHT strongly decreased the frequency of chromosome- but not of chromatid-type aberrations in G0/G1 and G1 and of chromatid-type aberrations in G2. These results are explained assuming that chromosome-type aberrations induced at G0/G1 and G1, and chromatid-type aberrations induced at G2 are originated by the induction of double-strand breaks by BLM through the formation of free radicals. Thus, the observed effect of BHT post-treatment could be considered as evidence that chromosome aberrations are induced by BLM following a two-step mechanism. On the other hand, it is necessary to differentiate between chromatid-type aberrations induced by BLM at G0/G1 and those produced by G2 treatment on the basis of replication errors for the former and DNA repair errors for the latter. In addition, the induction of chromatid-type aberrations by BHT itself at G0/G1 must be taken into account. As BHT acts as an S-dependent agent, chromatid-type aberrations observed after treatment with BLM and BHT in G0/G1 could arise from single-strand breaks induced by BLM and DNA primary lesions induced by BHT.

Animals↗
PubMed1997

Y-Chromosome morphology and incidence of the 1/29 translocation in argentine creole bulls.

The Argentine Creole is a local breed of cattle with high reproductive performance. This breed also shows resistance to many subtropical diseases. The cytogenetic status of the Argentine Creole, in particular the incidence of 1/29 translocation and Y-chromosome morphology, is not known in Argentina. Taking these factors into account, the cytogenetic study of 36 Argentinian Creole bulls was carried out. Heparinized blood samples were obtained and cultured for chromosome analysis. The results showed the absence of the 1/29 translocation in all the bulls analyzed and the presence of a submetacentric Y chromosome.

Journal Article↗
PubMed1996

Chromosomal aberrations in peripheral blood lymphocytes from native Andean women and children from northwestern Argentina exposed to arsenic in drinking water.

For conducting an adequate human cancer risk assessment of inorganic arsenic (As) in the low-dose region, it is important to establish its mode of action. In this context, the nature of genotoxic effects induced by this agent is of considerable interest. However, the results from such investigations in human have been conflicting. In an attempt to resolve this issue, the clastogenic and aneugenic potential of As was investigated in women and children from native population exposed to high levels (around 0.2 mg/l) of natural As via drinking water in San Antonio de los Corbes in the Andean region of Salta, Northwestern Argentina. The water did not contain elevated levels of heavy metals, such as lead or cadmium, nor was the investigated population exposed to significant industrial pollution or to pesticides. An ethnically similar control group from Rosario de Lerma, Salta, where only extremely low concentration of arsenic in drinking water could be detected, was used as a control. To evaluate the genotoxic effects in peripheral blood lymphocytes, micronuclei (MN) in binucleated cells, sister-chromatid exchanges (SCEs) and the fluorescence in situ hybridization technique (FISH) in combination with chromosome specific DNA libraries were employed. The data obtained clearly indicate a highly significant increase in the frequency of MN and of trisomy in lymphocytes from exposed children and women in comparison with controls, but no notable effects were found on the frequencies of SCEs, specific translocations, or on cell cycle progression. As supported by FISH analysis, at least a proportion of MN appears to originate from whole chromosome loss. An additional finding was the unusually low background levels of MN in unexposed individuals from this ethnic group as compared to other populations, e.g., Caucasians.

Adolescent↗
PubMed1996

Gene frequencies of DRB3.2 locus of Argentine Creole cattle.

Gene and genotype frequencies of BoLA-DRB3 were studied in seven herds of Argentine Creole cattle. Twenty-one out of thirty previously identified alleles were detected in this breed. The F statistics showed high degree of variability among the studied subpopulations suggesting that subdivision and genetic drift, rather than inbreeding, have been the major factors acting on the observed interpopulation variability. The observed high degree of genetic variation in Argentine Creole cattle could be crucial for the long-term survival of this population. Maintenance of such polymorphism, as a genetic resource, could be an important issue that will demand attention in future breeding programmes in species under high selective pressures.

Alleles↗
PubMed1995

The relation between protein malnutrition, ethanol consumption and chromosomal damage induced by cyclophosphamide in bone marrow cells of mice.

The effect of protein malnutrition and alcohol consumption on the yield of chromosomal damage induced by cyclophosphamide (CP) was studied. Chromosomal damage induced in bone marrow cells of BALB/c mice was established by scoring the frequency of dicentric chromosomes in C-banded slides. Results obtained showed that CP induced a significant increase of chromosomal damage in comparison with untreated mice. In addition, the yield of dicentric chromosomes was higher in mice fed with the hypoproteic diet. The animals which received ethanol in drinking water before treatment with CP exhibited the highest frequency of dicentric chromosomes, with no relation with the diet. Statistical analysis of these results showed the additive effect of diet and CP and are explained taking into account the metabolic pathways of CP as well as the decrease of enzymatic levels and the physiological condition in under-nourished mice.

Analysis of Variance↗
PubMed1993

The effect of a hypoproteic diet and ethanol consumption on the yield of chromosomal damage detected in bone marrow cells of mice.

The relationship between protein malnutrition and ethanol consumption as modulating factors of the genetic response to xenobiotics was studied. BALB/c mice of both sexes were fed for three weeks after weaning either with a normal diet containing 25% protein or a hypoproteic diet containing 5% protein. Half of the animals received 20% ethanol in drinking water. Cytogenetic analysis was performed in bone marrow cells. Slides were stained for C-banding in order to assure the accurate scoring of dicentric chromosomes. Results obtained showed an increased frequency of dicentric chromosomes in mice fed with the hypoproteic diet (5.45 dicentrics per 100 cells) in contrast to mice fed with the normal diet (0.61 dicentrics per 100 cells). Ethanol consumption increased the frequency of chromosomal damage, but no differences in the effect of ethanol between mice fed with the normal diet and mice fed with the hypoproteic diet (16.33 and 16.80 dicentrics per 100 cells respectively). The enhanced frequency of dicentric chromosomes in animals fed with the hypoproteic diet might have been originated from the increase or the improper repair of chromosome breaks. The similarity in the response to ethanol consumption in animals fed either with the normal or the hypoproteic diet might have been provoked by a decrease of alcohol dehydrogenase (ADH) level in undernourished mice. The chromosomal damage due to ethanol may be lower in undernourished mice than in mice fed with the normal diet due to the reduced amount of circulating acetaldehyde able to induce chromosomal damage. The results obtained are an evidence of the role played by the diet in the modulation of the genetic response to xenobiotics.

Alcohol Drinking↗
PubMed1990

The induction of reciprocal translocations in mouse germ cells by chemicals and ionizing radiations. II. Combined effects of mitomycin C or thio-tepa with two doses of gamma-rays.

The combined effects of mitomycin C (MMC) and thio-tepa (TT) with gamma-ray doses of 5 and 9 Gy on mouse stem cells were studied using the spermatocyte test. Both chemicals induced very low yields of translocations after single treatments. In combined treatments with a dose of 5 Gy, a subadditive effect of MMC and an additive effect of TT were found. Combined with a dose of 9 Gy the compounds potentiated the effect of radiations. Up to now, most of the chemicals tested have shown additive effects when combined with doses of the ascending part of the dose-response curve and potentiating effects when combined with doses of its descending part. This has been considered additional confirmation of the concept that depletion of any kind of spermatogonia is sufficient to modify the genetic response of stem cells. However, the subadditive and additive responses found could be considered evidence that common biological mechanisms can modulate the response to combined treatments of chemicals and ionizing radiations.

Animals↗