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1.
Four triazine herbicides: amitrole, metribuzin, prometryn and terbutryn, and the bipyridal compound diquat dibromide have been evaluated for genotoxicity in the wing somatic mutation and recombination test of Drosophila melanogaster, following standard procedures. Third-instar larvae trans-heterozygous for the third chromosome recessive markers multiple wing hairs (mwh) and flare-3 (flr(3)) were chronically fed with different concentrations of the test compounds. Feeding ended with pupation of the surviving larvae. Genetic changes induced in somatic cells of the wing's imaginal discs lead to the formation of mutant clones on the wing blade. Point mutation, chromosome breakage and mitotic recombination produce single spots; while twin spots are produced only by mitotic recombination. Exposure to 0.5 mM and 1 mM of amitrole clearly increased the frequency of small single, large single and total spots. Terbutryn, at the concentration of 5 mM, induced a slight increase in the frequency of small single and total spots, but this result could be false positive. The other three herbicides tested did not show any genotoxic effect. When heterozygous larvae for mwh and the multiple inverted TM3 balancer chromosomes were treated, significant increases in the frequency of mutant spots were only detected for amitrole. The observed spot frequencies were lower than those found in mwh/flr(3)50%) of the total spot induction was due to mitotic recombination.  相似文献   

2.
In the present study, the herbicides bentazone, molinate, thiobencarb and trifluralin were evaluated for mutagenic and recombinagenic effects using the wing spot test of Drosophila melanogaster (somatic mutation and recombination test, SMART). Both standard (ST) and high-bioactivation (HB) fly crosses were used, the latter cross is characterised by a high sensitivity to promutagens and procarcinogens. Three-day-old larvae, transheterozygous for the multiple wing hairs (mwh, 3-0.3) and flare-3 (flr(3), 3-38.8) genes, were chronically fed with six different concentrations of each herbicide. Feeding ended with pupation of the surviving larvae and the genetic changes induced in somatic cells of the wing's imaginal discs lead to the formation of mutant clones on the wing blade. Point mutation, chromosome breakage and mitotic recombination produce single spots; while twin spots are produced only by mitotic recombination. Bentazone, usually considered as a non-mutagen, gave positive results in the wing spot test with the high-bioactivation cross. Molinate, about which information on mutagenic effects is inconclusive, gave positive responses in both the standard and the high-bioactivation crosses, while the other thiocarbamate, thiobencarb, gave positive results only in the standard cross and at the highest concentration tested (10 mM). Finally, trifluralin, one of the most widely studied herbicides for genotoxic effects, gave positive results in the wing spot test with both crosses. Apart from the interest of the results found in the genotoxic evaluation of the four selected herbicides, our results also contribute to extend the existing database on the Drosophila wing spot test, and corroborate the utility of the use of high-bioactivation strains for the genotoxic evaluation of xenobiotics.  相似文献   

3.
The effect of a tumor promoter, 12-O-tetradecanoyl-phorbol 13-acetate (TPA) alone and in combination with mitomycin C (MMC) or cyclophosphamide (CPP) on the induction of sister-chromatid exchanges (SCE) in Chinese hamster V79 cells was investigated. TPA alone at various doses and durations caused no increase of SCE frequency. MMC either at the dose of 0.03 or 0.003 μg/ml alone or in combination with TPA (2 μg/ml) all caused a significant increase of SCE frequencies. There was no difference in SCE frequencies between the cultures treated with MMC alone at 0.03 μg/ml and those treated with MMC plus TPA. However, cultures treated with MMC at 0.003 μg/ml plus TPA had significantly and consistently higher SCE frequencies than those treated with MMC alone at all durations. Treatment of CPP at 1 μg/ml activated by S9 mix caused significant increase of SCE frequencies. Surprisingly, the cultures treated with CPP, S9 mix plus TPA (2 μg/ml) caused a drastic reduction of SCE frequencies as compared to those treated with CPP and S9 mix only at all durations. These results indicate that TPA alone had no effect on SCE in V79 cells. TPA enhanced the SCE induction in V79 cells treated with MMC at a low dose, i.e. 0.003 μg/ml, but it inhibited SCE induction in cultures treated with the indirect mutagen CPP. Thus, TPA has no direct effect on genetic materials but it may indirectly alter the effects of a mutagen.  相似文献   

4.
The state of aneuploidy test methodology was appraised by the U.S. Environmental Protection Agency in 1986 in analyzing published data. In Saccharomyces cerevisiae 9 chemicals were reported to be conclusive positive for aneuploidy induction in either mitotic or meiotic cells. We reevaluated these 9 chemicals using Saccharomyces cerevisiae D61.M, a strain that detects mitotic chromosome malsegregation. Acetone (lowest effective dose (LED): 40 microliters/ml), bavistan (LED: 5 micrograms/ml), benomyl (LED: 30 micrograms/ml) and oncodazole (LED: 4 micrograms/ml) induced a dose-dependent increase in the frequencies of chromosomal malsegregation. Ethyl methanesulfonate (EMS; highest tested dose (HTD): 1000 micrograms/ml) and methyl methanesulfonate (MMS; HTD: 100 micrograms/ml) did not induce malsegregation but were both potent inducers of other genetic events, detected by an increase in the frequencies of cyhR cells. No increases in both endpoints (malsegregation and other genetic events) were observed after treatment of S. cerevisiae D61.M with cyclophosphamide (CP; HTD: 16 mg/ml) in the absence of S9, p-D,L-fluorophenylalanine (p-FPA; HTD: 250 micrograms/ml) and phorbol-12-myristate-13-acetate (TPA; HTD: 50 micrograms/ml). A marginal increase in the frequency of mitotic chromosome malsegregation was obtained with cyclophosphamide in the presence of S9. Thus our test results largely disagree with those previously published by various authors and taken as conclusive by EPA. We interpret the discrepancies to be due to lack of properly controlled testing (e.g., no check for multiple mutational events). Only with a careful test design it is possible to discriminate between chemicals inducing only chromosome loss and no other genetic effects (e.g., acetone, oncodazole), chemicals inducing a variety of genetic damage but no chromosome loss (e.g., EMS, MMS) and chemicals inducing neither chromosome loss nor other genetic events in yeast (e.g., TPA, p-FPA).  相似文献   

5.
The tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) does not increase the sister-chromatid exchange (SCE) frequency in either Chinese hamster ovary (CHO) or lung (V 79) cells which are cultured in the presence of 5-bromodeoxyuridine. Moreover, TPA does not alter the induction of SCEs in CHO cells by mitomycin C during the first 3 cycles following addition of the alkylating agent. These SCE induction data do not by themselves support the hypothesis that tumor promotion by TPA depends on the enhancement of mitotic recombination.  相似文献   

6.
黄芫花提取物对V79细胞和WB肝细胞的生物...:1....   总被引:3,自引:0,他引:3  
A Chinese herb, wikstroemia Chamaedaphen (WC) extract, recently has been shown to be a potential tumor promoting agent on uterine cervical carcinoma induced by HSV-2 or MCA in mice. To determine whether the tumor promoting effects of WC extract were mediated through inhibition of gap junctional intercellular communication (GJIC) with relation to cellular growth, experiments were conducted on Chinese hamster V79 cells and rat WB liver cells by utilization of SLDT method for GJIC detection and cell growth curve examination, 3H-TdR incorporation, mitotic index (MI) and Flow Cytometry (FCM) methods. TPA was used for comparative purpose. WC extract inhibited GJIC and stimulated cell growth in a dose (2-200 micrograms/ml) and time (0-72 hr)-dependent manner in both cell lines. Both WC extract and TPA treatments increased V79 cell growth rate. The average cell doubling-time was decreased from 36.5 hr in control V79 cells to 28.2 hr in WC extract (10 micrograms/ml) and 20.9 hr in TPA (50 ng/ml) treatment by the 3rd day. Stimulating effect of both drugs on DNA synthesis of V79 cells was demonstrated. The results of FCM and MI indicated that the cell number of M-phase cells was increased after drug treatment. It is suggested that (1) tumor promoting effect of WC extract might be mediated through inhibition of GJIC: (2) inhibition of GJIC is closely correlated with increased cell growth rate and entry of cell division cycle.  相似文献   

7.
A J Katz 《Mutation research》1987,192(2):131-135
The fumigant methyl bromide was evaluated for genotoxicity in the somatic wing-spot assay of Drosophila melanogaster. Third instar larvae trans-dihybrid for mwh and flr3 were exposed to varying concentrations (0-16 mg/l) of the gas for 1 h. Following this exposure via inhalation, the larvae were placed into vials containing Instant Medium. 7 days after the exposure, the adult flies in the vials were collected, and their wings were scored under 400X magnification for the presence of clones of cells possessing malformed wing-hairs. Such clones appeared as mwh-flr3 twin spots and single spots of either mwh or flr3 phenotype. Exposure to methyl bromide was found to result in the positive induction of both twin spots and large (greater than 2 cells) single spots. For each endpoint, a significant exponential association was obtained between concentration and frequency of spots per wing. Methyl bromide was found to be a negative inducer of small (1-2 cells) single spots at all concentrations except 16 mg/l where a positive effect was observed. Because twin spots arise exclusively from mitotic recombination, methyl bromide was identified as having recombinogenic activity in the somatic tissue of Drosophila larvae.  相似文献   

8.
Summary In first and second instar larvae of Drosophila melanogaster mitotic recombination has been induced by X-rays. Resulting mosaic spots were analysed in the eyes of adult females. The five examined genotypes varied in the combination of different X-chromosomes and in the presence or absence of the duplication Dp(1;3)N 264-58. X-chromosomes used have been elongated by proximally or distally linked arms of the Y-chromosome. The portion of Y-heterochromatin in the genome is negatively correlated with the frequency of twin mosaic spots (Fig. 1). The frequency of these spots is lower in flies bearing the duplication than in those without the duplication. With respect to the X-chromosome combinations, there are no marked differences in the frequencies of single mosaic spots (Fig. 2); with respect to the duplication they are absent. In the genotype Y S X/X.Y S prophases of neuroblast mitoses (Fig. 4) show normal pairing of homologous chromosome sections. Reasons for the different spot frequencies are discussed.

Vorgelegt von E. Hadorn  相似文献   

9.
Investigation of the potential for mitotic recombination in the mouse   总被引:2,自引:0,他引:2  
A variation of the mouse spot test is described that is designed to distinguish between spots of altered coat colour that arise by reciprocal mitotic recombination and those caused by somatic mutation or non-disjunction. Mouse fetuses that were heterozygous for two, linked coat colour genes were irradiated (1.5 Gy X-rays) in utero at 10.25-10.50 days post coitum (p.c.) or left untreated. Subsequently, the coats were classified for the presence of spots of altered colour. The irradiated embryos were heterozygous for the linked genes pink-eyed dilution (p) and albino (c) and were produced by both the repulsion and coupling crosses. Half of the reciprocal recombination events between the centromere and the proximal marker (p), in heterozygotes with p and c in repulsion, should produce twin spots. No such twin spots would be expected from a similar event in the coupling heterozygotes. The coats of 238 irradiated and 208 untreated repulsion heterozygotes plus 107 irradiated and 314 untreated coupling heterozygotes were classified for spots. One irradiated, repulsion heterozygote had a diffuse twin spot that was only recognisable by microscopic examination of the hairs. We conclude that if the treatment described induces mitotic recombination in the mouse, it does so with low efficiency.  相似文献   

10.
Teratogenic effect of two mitotic poisons, griseofulvin and colchicine, was confirmed. A similar effect of another antimitotic agent, vinblastin, was demonstrated. The teratogenic effect of these poisons is expressed as a reduction of ommatidia in adult flies when the drug is fed to larvae. The highest frequency of phenocopies was recorded in temperature- and mutagen-sensitive strains. The mutagenic activity of vinblastin and griseofulvin was confirmed by the wing-spot test (somatic mutation and recombination test, SMART) in Drosophila melanogaster. In addition, this test demonstrated mutagenic activity of colchicine. All of the mitotic poisons induced small single spots but did not increase frequency of twin spots mwh/flr. Spot frequency was significantly higher in mutagen-sensitive mutants having defective excision repair. Heat shock (45-min exposure at 37 degrees C) decreased the frequency of phenocopies induced by the mitotic poisons. When third-instar larvae were subjected to heat shock prior to drug administration, the frequency of mutant cell clones was significantly reduced. These results indicate participation of heat-shock proteins in the protection of microtubules in actively proliferating cells of D. melanogaster.  相似文献   

11.
12-O-Tetradecanoylphorbol-13-acetate (TPA) is a well-known tumor promoter in mouse-skin carcinogenesis. Its effects on mutagenesis in a soybean test system were examined, and the effects were judged from the appearance of spots of various colors on the leaves. When soybean seeds were treated with TPA plus 0.03% caffeine, the frequency of spots per leaf decreased significantly and in proportion to the concentration of TPA. TPA alone at concentrations of 1–20 μg/ml did not induce any mutations. Mutations induced by γ-rays were not affected by administration of TPA either before or after exposure to γ-rays. The mechanism of suppression by TPA of mutations induced by caffeine is discussed.  相似文献   

12.
DNA breaks and repair in mouse leukemia L1210 cells treated with 3 different types of cross-linkers, mitomycin C (MMC), 1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitroso ure a hydrochloride (ACNU) and SN-07 (a macromolecular antibiotic), were studied. Measured in D37 values, MMC gave the highest number of cross-links per lethal 'hit' directly after the 1-h treatment in the alkaline elution assay, followed by ACNU and SN-07. A good dose-response increase in induced interstrand DNA cross-linking frequency was observed in cells treated with 2.5-10 micrograms/ml MMC and with 10-100 micrograms/ml ACNU for 1 h with and without 24-h post-incubation. After 6-h post-incubation, the highest frequency of cross-linking was observed in cells treated with 2.5 micrograms/ml MMC and 30 micrograms/ml ACNU, while cross-link production continued in the cells treated with SN-07 for 12-h post-incubation. No significant increase in DNA breaks was observed in cells treated with MMC throughout 24-h post-incubation. The highest frequency of single-strand DNA breaks in cells treated with ACNU was observed immediately after the treatment and they disappeared after 6-h post-incubation. After 24-h post-incubation, a marked enhancement of the DNA breaks was observed in cells treated with SN-07 and the cells contained double-strand DNA breaks also. RNA synthesis was not affected in the cells treated with 10 micrograms/ml MMC and slightly inhibited to 70% of control in those treated with 100 micrograms/ml ACNU, while DNA synthesis in both cells was significantly inhibited after 24-h post-incubation. By contrast, both RNA and DNA synthesis were completely inhibited in cells treated with 8.0 micrograms/ml SN-07.  相似文献   

13.
Genotoxicity of 5-azacytidine in somatic cells of Drosophila   总被引:1,自引:0,他引:1  
A J Katz 《Mutation research》1985,143(3):195-199
The newly developed somatic mutation and recombination test, utilizing the wing-hair mutations mwh and flr3, was used to evaluate the genotoxicity of the base analog 5-azacytidine in larvae of Drosophila melanogaster. Third instar larvae were fed media wetted with various concentrations of the compound, and wings of surviving adults were removed and scored for the presence of clones of cells possessing malformed hairs. Wings of exposed flies trans-dihybrid for mwh and flr3 had significantly increased frequencies of twin spots, small single spots and large single spots. Significant linear regression of twin-spot frequencies upon concentration was also obtained. Induction of twin spots by 5-azacytidine unambiguously demonstrates its recombinogenic activity in somatic cells of Drosophila. Significantly increased frequencies of large single spots on wings of inversion-heterozygous flies were also observed and suggest that 5-azacytidine may also be inducing somatic gene mutations (or deletions).  相似文献   

14.
Treatment of human promyelocytic leukemia cells (HL-60 cells) with 12-O-tetradecanoylphorbol 13-acetate (TPA) results in terminal differentiation of the cells to macrophage-like cells. Treatment of the cells with TPA induced marked enhancement of the phosphorylation of 28- and 67-kDa proteins and a decrease in that of a 75-kDa protein. When the cells were treated with diacylglycerol, i.e. 50 micrograms/ml 1-oleoyl-2-acetylglycerol (OAG), similar changes in the phosphorylation of 28-, 67-, and 75-kDa proteins were likewise observed, indicating that OAG actually stimulates protein kinase C in intact HL-60 cells. OAG (1-100 micrograms/ml), which we used, activated partially purified mouse brain protein kinase C in a concentration-dependent manner. Treatment of HL-60 cells with 10 nM TPA for 48 h caused an increase by about 8-fold in cellular acid phosphatase activity. Although a significant increase in acid phosphatase activity was induced by OAG, the effect was scant compared to that of TPA (less than 7% that of TPA). After 48-h exposure to 10 nM TPA, about 95% of the HL-60 cells adhered to culture dishes. On the contrary, treatment of the cells either with OAG (2-100 micrograms/ml) or phospholipase C failed to induce HL-60 cell adhesion. Ca2+ ionophore A23187 failed to act synergistically with OAG. In addition, hourly or bi-hourly cumulative addition of OAG for 24 h also proved ineffective to induce HL-60 cell adhesion. Our present results do not imply that protein kinase C activation is nonessential for TPA-induced HL-60 cell differentiation, but do demonstrate that protein kinase C activation is not the sole event sufficient to induce HL-60 cell differentiation by means of this agent.  相似文献   

15.
The effects of a tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) and/or an anti-promotor antipain (protease inhibitor) on spontaneous and ultraviolet-induced sister-chromatid exchanges (SCEs) and 6-thioguanine- resistant (6TGr) recessive mutations were examined in V79 Chinese hamster cells in culture. TPA and/or antipain neither significantly altered base-line and UV-induced immediate SCE frequencies, nor decreased the level of delayed SCEs which persisted 6–7 days after irradiation. TPA and/or antipain appeared to enhance the recovery of UV-induced 6TGr colonies at the plateau expression phase despite non-mutagenicity by themselves and unaltered metabolic co- operation. Thus, the results conceivably imply that the 6TGr-recessive mutation expression, but not fixation, can be modulated at the cell level by the TPA and/or antipain. Our results, together with the recent results of Loveday and Latt, may argue against the notion that TPA enhances the antipain-suppressible SCEs as an index of mitotic recombination in relevance with a tumor-promotion mechanism.  相似文献   

16.
In studies on the mechanisms of mutagenic and carcinogenic action of captan and captafol-related chloroalkylthiocarboximide fungicides, two effects were tested: (i) the effect of both compounds on the activity of eukaryotic topoisomerases I and II in vitro, and (ii) their mutagenic and recombinagenic activity in the somatic mutation and recombination test (SMART) in wing cells of Drosophila melanogaster. Only captafol inhibited the activity of topoisomerase I (10-20% inhibition of activity in the range of 10-100microM). In contrast, both chemicals decreased the activity of topoisomerase II already at 1microM concentration (50 and 20% inhibition of activity by captafol and captan, respectively).Genotoxicity was tested in vivo by administrating both compounds by acute (3h) and chronic feeding (48h) of 3-day-old larvae. In acute feeding, captan and captafol demonstrated positive results only for small single and total spots in 10-100mM exposure concentration range. Both chemicals were inconclusive for large single spots, as well as for twin spots. In chronic treatment, captan showed positive results only for small single and total spots at 2.5 and 5mM concentrations. Captafol gave inconclusive results over all concentrations tested. The results of the acute treatment experiments which have been performed at very high doses (50% toxicity at higher doses) indicate very weak overall mutagenic activity of both test fungicides.  相似文献   

17.
Summary Mitotic recombination has been induced with X-rays in Drosophila melanogaster larvae and assayed later as twin mosaic spots in the adult eyes. When the X-chromosomes are marked with zeste and white and the third chromosomes with roughoid and sepia, the frequency of twin spots was about 20 times higher for the X-chromosome than for the third chromosome. The greater amount of heterochromatin in the X-chromosome was considered responsible for the difference.Experiments with different inversion heterozygotes support this interpretation. Euchromatic inversions of different lengths have, when heterozygous, little or no influence on the twin spot frequency. The shorter the heterochromatic segment between the kinetochore and the proxomal break point of the inversion the stronger is the reduction of the twin spot frequency.The heterozygotes for the long sc 8 and sc S1 inversions gave exceptionally low twin spot frequencies. It seems possible that potential twin spot daughter cells die after recombination because of genetic imbalance and/or lack of proper cell separation resulting from the persistence of the dikinetic chromosome elements.To test whether inaccurate somatic pairing in inversion heterozygotes could help explain the low twin spot frequencies in those of sc 8 and sc S1, neuroblast chromosomes were investigated. They show that chromosomal arrangement during metaphase is determined exclusively by the location of the kinetochore, which always points, irrespective of earlier somatic pairing, toward the center of the metaphase plate. It is possible that there is a lack of proper chromosome alignment at the X-ray sensitive stage for mitotic recombination.  相似文献   

18.
A stable staining procedure of sister-chromatid differentiation (SCD) using a monoclonal antibromodeoxyuridine (BrdU) antibody was newly established by combining it with the immunoperoxidase reaction (3,3'-diaminobenzidine, DAB reaction). This procedure permitted detection of SCD and SCE at very low BrdU concentrations. SCD was not usually observed below 2.0 micrograms/ml BrdU with flame-dried chromosome slides. When chromosome slides were prepared by air-drying over 37 degrees C warm water, SCD was detected at 10.0, 5.0, 1.0, 0.5, 0.3 and 0.2 micrograms/ml BrdU with FPG and even at 0.1 microgram/ml BrdU with the antibody technique. SCE levels were evaluated using the antibody technique and endomitotic analysis with FPG at low BrdU concentrations (1.0, 0.5, 0.3, 0.2 microgram/ml) in two BS B-lymphoblastoid cell lines (LCLs). Even though the BS SCE level was approximately 70 per cell at 10 micrograms/ml, the value decreased to the level of 20-30 SCE per cell at 0.1 microgram/ml with the antibody technique. In BrdU-labelled BS endomitoses, single SCEs highly decreased with BrdU concentrations (130-140 level at 10 micrograms/ml: 38-60 level at 0.2 microgram/ml), when compared to the rare twin SCE values (3-6 SCE level) at all BrdU concentrations. These findings conclusively indicate that the spontaneous baseline SCE in BS B-lymphoblastoid cells is low and most BS SCEs are caused by BrdU.  相似文献   

19.
Phytohemagglutinin (PHA), picibanil (OK432) and tumor promoting agent (TPA) were tested in various combinations for optimal induction of human interferon-gamma (HuIFN-gamma). It was found that the use of a mixture of all 3 inducers resulted in IFN production 2-3 times higher than either PHA (10 micrograms/ml) in combination with TPA (5 ng/ml) or picibanil (10 micrograms/ml) alone. The IFN was produced by T lymphocytes and could be neutralized by specific IFN-gamma antiserum. It was pH 2.0 labile and species specific.  相似文献   

20.
Chios mastic gum, a plant-derived product obtained by the Mediterranean bush Pistacia lentiscus (L.) var. chia (Duham), has generated considerable interest because of its antimicrobial, anticancer, antioxidant and other beneficial properties. Its aqueous extract, called Chios mastic water (CMW), contains the authentic mastic scent and all the water soluble components of mastic. In the present study, the potential genotoxic activity of CMW, as well as its antigenotoxic properties against the mutagenic agent mitomycin-C (MMC), was evaluated by employing the in vitro Cytokinesis Block MicroNucleus (CBMN) assay and the in vivo Somatic Mutation And Recombination Test (SMART). In the former assay, lymphocytes were treated with 1, 2 and 5% (v/v) of CMW with or without MMC at concentrations 0.05 and 0.50 µg/ml. No significant micronucleus induction was observed by CMW, while co-treatment with MMC led to a decrease of the MMC-induced micronuclei, which ranged between 22.8 and 44.7%. For SMART, larvae were treated with 50 and 100% (v/v) CMW with or without MMC at concentrations 1.00, 2.50 and 5.00 µg/ml. It was shown that CMW alone did not modify the spontaneous frequencies of spots indicating lack of genotoxic activity. Τhe simultaneous administration of MMC with 100% CMW led to considerable alterations of the frequencies of MMC-induced wing spots with the total mutant clones showing reduction between 53.5 and 74.4%. Our data clearly show a protective role of CMW against the MMC-induced genotoxicity and further research on the beneficial properties of this product is suggested.  相似文献   

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