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A Creus

Publications and source records attributed to A Creus.

At least 73 records · Page 4Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

The effect of cytochalasin-B concentration on the frequency of micronuclei induced by four standard mutagens. Results from two laboratories.

In a previous collaborative work, we have recently shown that the cytochalasin-B (Cyt-B) concentration used in the human lymphocytes cytokinesis-block micronucleus (CBMN) assay is an important variable in the baseline micronuclei (MN) frequency as well as in the percentage of binucleated cells obtained. Now we have investigated how Cyt-B concentration modulates the MN frequency induced in whole blood human lymphocyte cultures by two clastogens (ethyl methanesulphonate and mitomycin-C) and two aneugens (colchicine and vincristine sulphate). The experimental design includes six donors, two concentrations of Cyt-B (3 and 6 micrograms/ml), two concentrations of the four chemicals tested and the exchange of slides between laboratories. The statistical analysis of the results shows: (i) non-significant differences in the MN frequencies and in the toxicity results between scorers from each laboratory, except for 0.06 microM colchicine at 3 micrograms/ml Cyt-B; (ii) an induction of MN by all genotoxic agents tested, the frequencies being lower with 6 than with 3 micrograms/ml Cyt-B, in control and aneugen-treated cultures; and (iii) significant differences between Cyt-B concentrations in several treatments, obtaining lower MN frequencies and higher values for nuclear division index and % binucleated cells when 6 micrograms/ml Cyt-B was used. Bearing in mind these results as well as the toxicity data showing that 6 micrograms/ml Cyt-B is much more effective in blocking cytokinesis, we can conclude that the use of 3 micrograms/ml Cyt-B may overestimate the induced frequency of MN.

Adult↗

Cytogenetic biomonitoring in a Spanish group of agricultural workers exposed to pesticides.

Sister chromatid exchanges (SCE) and chromosome aberrations (CA) were studied in the lymphocytes of 70 male agricultural workers occupationally exposed to several pesticides and 69 matched controls, without indication of exposure to pesticides, from 'El Maresme' (Barcelona, Spain), Comparison between both groups revealed that the individuals exposed to pesticides show substantial clastogenic effects in their lymphocytes without indication of increases in the basal frequency of SCE; moreover, these effects seem to be additive, increasing with the duration of exposure measured in years. When two confounding factors such as age and smoking habits are considered, we found that these factors increase significantly the expression of SCE although no effect was detected in the expression of CA.

Age Factors↗

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↗

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↗

Genotoxicity studies with the unstable zeste-white (UZ) system of Drosophila melanogaster: results with ten carcinogenic compounds.

To increase the number of chemicals tested using the zeste-white (UZ) somatic mutation assay, ten selected carcinogens (acetamide, acrylamide, benzo(alpha)pyrene, cyclophosphamide, diethylstilbestrol, 4-nitroquinoline N-oxide, propyleneimine, safrole, thiourea, and o-toluidine) have been evaluated in this assay. Our results show that all the compounds tested produce significant increases in the eye spot frequency at, at least, one of the concentrations assayed, indicating that the zeste-white assay appears to be highly sensitive to these carcinogenic compounds. That is in agreement with data previously reported by other authors.

4-Nitroquinoline-1-oxide↗

Additional data in support of the quadruplicated white-ivory reversion system to test for somatic genotoxicity in Drosophila melanogaster.

Cyclophosphamide, ethyl methanesulfonate, propyleneimine and tritiated water were tested in a new short-term somatic mutation bioassay, previously described by Green and coworkers (1986), to evaluate the suitability of the quadruplicated white-ivory system of Drosophila melanogaster for genotoxicity testing of chemicals. A 2.9-kb tandemly duplicated sequence of w+ within a w+ gene is responsible for the white-ivory phenotype. Reversion of wi to w+ is, in general, associated with the loss of the appended 2.9 kb or other alterations affecting this duplicated region. The appearance of light (white or nearly white) phenotypes could be due to the loss of some wi copies. Thus, in the eyes of adult males resulting from treated larvae, we can detect 2 types of sectors (red and light) on the orange-yellow background. Our results indicate that the genetic system used in this somatic assay is sensitive to the genotoxic effects of the 4 compounds tested. All 4 compounds tested were positive. Tritiated water had weak effects, cyclophosphamide was characterized by small revertant clones and ethyl methanesulfonate and propyleneimine by large clone size. From the available data, we feel that the wi system can be considered of potential value for genotoxicity testing.

Animals↗

Induction of mitotic micronuclei by the pyrethroid insecticide fenvalerate in cultured human lymphocytes.

The pyrethroid insecticide fenvalerate was tested for its ability to induce mitotic micronuclei in cytokinesis-block cells of cultured human peripheral blood lymphocytes at concentrations ranging from 10 to 50 micrograms/ml. We observed that fenvalerate induces a significant increase in the frequency of micronuclei, indicating clastogenic and/or aneugenic activity. Our results complement previous data on the genotoxicity of this compound in human lymphocytes.

Alkylating Agents↗

Mutagenic evaluation of the organophosphorus insecticides methyl parathion and triazophos in Drosophila melanogaster.

The possible genotoxic effects of the organophosphorus insecticides methyl parathion and triazophos were evaluated by their ability to induce gene and chromosome mutations in male germ cells of Drosophila melanogaster. Sex-linked recessive lethal (SLRL), total and partial sex-chromosome losses (SCL), and non-disjunction (ND) assays were conducted. The routes of administration included adult feeding, injection, and larval feeding. Methyl parathion was unable to induce point mutations or chromosome mutations, although a small increase in the frequency of non-disjunction was detected after larval treatment. Triazophos induced point mutations when assayed in the SLRL test and induced a weak increase in the non-disjunction frequency, but gave negative results in the SCL test.

Animals↗

Sister chromatid exchange in lymphocytes of agricultural workers exposed to pesticides.

Sister chromatid exchange (SCE) was studied in the lymphocytes of 27 agricultural workers occupationally exposed to several pesticides and 28 matched controls from el Maresme, an agricultural area near Barcelona. Comparison between both groups with the t-test did not reveal significant differences. These negative findings suggest that, possibly, the exposure level is too low to increase SCE in human lymphocytes in vivo. Our results indicate that smokers, both the workers and the controls, had a higher SCE frequency than non-smokers, in agreement with previous data reported by different authors.

Adult↗

Mitotic arrest induced by fenvalerate in human lymphocyte cultures.

The pyrethroid insecticide fenvalerate was tested for its ability to induce C-mitosis in cultured human peripheral blood lymphocytes at concentrations ranging from 2-50 micrograms/ml. We observed a significant increase in C-mitotic figures, indicating that this compound was effective in producing disturbance of spindle function.

Cells, Cultured↗