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Results for “Micronucleus Tests”

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At least 109 records · Page 6Linked to original sources

PubMed1999

Validation study of the in vitro micronucleus test in a Chinese hamster lung cell line (CHL/IU).

We conducted a collaborative validation study, under the auspices of the Japanese Ministry of Labour, on the in vitro micronucleus test to see if it could be used as an alternative to the in vitro chromosome aberration test for evaluation of chemical safety. We used the Chinese hamster lung cell line (CHL/IU), which is the most widely used system for the latter test in Japan, and evaluated 66 chemicals, including clastogens and polyploidy inducers. The cytochalasin B cytokinesis blocking method, which is commonly used in human lymphocyte culture, was applied to the established cell line, but did not improve the detection of chemically-induced micronuclei in continuously growing cells. The highest micronucleus frequencies were obtained at 48 or 72 h continuous treatments. In short treatments (6 h), a 42 h recovery time yielded the best responses. Concordance between the results of the micronucleus test and the chromosomal aberration test was satisfactorily high (88.7%), and we concluded that the in vitro micronucleus test could be used in place of the chromosomal aberration test as a simple and rapid method for detecting clastogens and aneugens in vitro. We also propose a protocol for the test.

Animals↗

PubMed1989

Micronucleus test with methyl methanesulfonate administered by intraperitoneal injection and oral gavage.

The effects of 2 routes of administration, intraperitoneal injection (i.p.) and oral gavage (p.o.), in the micronucleus test were evaluated using methyl methanesulfonate (MMS) and 2 strains of mice (MS/Ae and CD-1). A small-scale acute toxicity study and a pilot micronucleus experiment were carried out first. On the basis of the results obtained, a final micronucleus test was performed at doses of 20, 40, 80, and 160 mg/kg (i.p.) and 40, 80, 160, and 320 mg/kg (p.o.), with a 24-h sampling time. MMS induced micronucleated polychromatic erythrocytes (MNPCEs) in both routes in both mouse strains under the conditions used. At 40 and 80 mg/kg, MMS induced a higher number of MNPCEs by the i.p. route in both strains. A 160 mg/kg MMS dose induced higher numbers of MNPCEs by the p.o. route in MS/Ae mice. The route-related difference with MMS on the basis of mg/kg disappeared when the difference was determined on the basis of a ratio of the LD50. In practice, both i.p. and p.o. routes are acceptable as routes of administration in the micronucleus test using this chemical.

Administration, Oral↗

PubMed2003

Micronucleus test in freshwater fish species: an evaluation of its sensitivity for application in field surveys.

Brown trout, Salmo trutta, European eel, Anguilla anguilla, and European minnow, Phoxinus phoxinus, three fish species inhabiting European freshwater ecosystems, were evaluated for their use as in situ pollution biomarkers using the micronucleus test in renal erythrocytes. Experimental exposure (by immersion) to different concentrations of cyclophosphamide, colchicine, and cadmium showed that brown trout are more sensitive to the three compounds than minnows and eels. In situ surveys of wild freshwater ecosystems with different levels of pollution showed that minnows and eels living in polluted sites do not present higher micronuclei averages than those caught in clean rivers systems, whereas micronuclei are induced in brown trout inhabiting polluted sites. Our results demonstrated the suitability of brown trout for in situ biomonitoring of freshwater ecosystems as well as for laboratory tests using the micronucleus test.

Anguilla↗

PubMed1995

Comparative mutagenicity of 2-methylpropene (isobutene), its epoxide 2-methyl-1,2-epoxypropane and propylene oxide in the in vitro micronucleus test using human lymphocytes.

2-Methylpropene (isobutene), a gaseous compound widely used in chemical industries, is metabolized to the epoxide 2-methyl-1,2-epoxypropane. The parent compound has previously been shown to be non-mutagenic in a modified Ames test, whereas the epoxide metabolite gave a positive result. In this study, both compounds have been tested in the in vitro micronucleus test using human lymphocytes. Propylene oxide, a well known mutagenic compound, served as a positive control. It was found that 2-methylpropene had no mutagenic effect, whereas its epoxide induced a statistically significant dose-dependent increase in the number of micronuclei. The effect observed was comparable with that obtained for propylene oxide.

Alkenes↗

PubMed1989

A procedure for data analysis of the rodent micronucleus test involving a historical control.

No standard procedure of data analysis for rodent micronucleus tests involving historical controls has been established. In the present paper, under the presumption that the distribution of the historical control is stable and reliable, a procedure with three statistical steps is proposed to analyze the frequency of micronucleated polychromatic erythrocytes (MNPCEs). In the first step, the frequencies of MNPCEs in negative and positive control groups of a current experiment of the micronucleus test are compared with the distribution of historical negative and positive controls to examine the technical validity of the current experiment. In the second step, the frequency of MNPCEs in each treatment group is compared with the distribution of the historical negative control. In the third step, the dose-response relation is tested with the Cochran-Armitage trend test. A Monte Carlo stimulation study shows that the power of this procedure is acceptable and also this procedure is robust. An application of this procedure on real data reveals that it is effective in detecting clastogenic chemicals when the probability of a type I error is nearly .01.

Animals↗

PubMed1995

[Use of the micronucleus test for biological dosimetry in cases of homogeneous or non-homogeneous exposure to ionizing radiations].

The dose effect relationship after homogeneous irradiation and the effect on the Poisson distribution of adding non-irradiated blood and thereby simulating non homogenous accidental exposure were studied for dicentric aberrations and micronuclei in lymphocytes exposed in vitro to 60Co gamma irradiation. The dose effect relationship for both parameters was of the linear quadratic type with the micronuclei responding slightly less to radiation than the dicentrics but a greater number of cells can easily be screened for micronuclei than for dicentrics. Except for one dose level in micronuclei, no deviations from the Poisson distribution were observed, after homogeneous tradition, but such a deviation was evident when non-irradiated blood was added to the irradiated one. With the help of the method of the "contaminated Poisson distribution" the proportion as well as the dose of the exposed blood could be approximately estimated. In order to test the suitability of the micronucleus test in vivo, both dicentrics and micronuclei were determined in patients treated for seminoma to an abdominal field. The data showed a consistent increase in both parameters without a significant difference between patients. The increase of both types of anomalies corresponded about to that expected from the size of the field exposed. The data from micronuclei appear, therefore, about as reliable for biological dosimetry as those from dicentrics for biological dosimetry after homogeneous and non-homogeneous exposure to ionizing radiations.

Adult↗

PubMedDate not supplied

The micronucleus test of benzo[a]pyrene with mouse and rat peripheral blood reticulocytes.

The micronucleus test using peripheral blood reticulocytes (RETs) was evaluated in CD-1 and BDF1 mice and Sprague-Dawley rats treated with benzo[a]pyrene at two independent laboratories. The maximum incidence of micronucleated reticulocytes (MNRETs) appeared in both strains of mice 48 h after the treatment; interlaboratory differences were small. The incidence of MNRETs in BDF1 mice was higher than in CD-1 mice. In rats, significant increases of MNRETs with the maximum response at 72 h were detected when B[a]P was administered i.p.; slight but significant increases were observed at 24 h or later, with the maximum at 24-48 h, when it was administered p.o. These results suggest that the new method for the micronucleus test using circulating RETs will be useful in the detection of the clastogenicity of chemicals.

Animals↗

PubMed1989

Micronucleus test with procarbazine hydrochloride administered by intraperitoneal injection and oral gavage.

The difference in effect of route of administration of procarbazine hydrochloride (PCZ) in the mouse was investigated in the micronucleus test. PCZ was administered by intraperitoneal injection (i.p.) and oral administration (p.o.) to 2 strains of male mice (MS/Ae and CD-1). On the basis of a small-scale acute toxicity test and a pilot micronucleus test, bone marrow preparations were prepared 24 h after the administration by the i.p. and p.o. routes of 50-400 mg/kg and 200-1600 mg/kg, respectively. The maximum incidence of polychromatic erythrocytes with micronuclei (MNPCEs) was somewhat higher after p.o. treatment in MS/Ae mice and the same with both routes in CD-1 mice. Thus, the clastogenicity of PCZ in mouse bone marrow was revealed by both routes.

Administration, Oral↗

PubMed1997

Heavy metal content and mutagenic activity, evaluated by Vicia faba micronucleus test, of Tiber river sediments.

Tiber river sediment samples, collected in October 1995, were tested for mutagenicity by the micronucleus test in Vicia faba root tips. Four stations were studied within the urban area of Rome: (1) Castel Giubileo, at the entry of the urban area; (2) Ponte Tor di Quinto, immediately after the confluence of the tributary river Aniene; (3) Ponte Sublicio, in the middle of the city; and (4) Ponte della Magliana, immediately outside Rome, 20 km from the sea. Since no significant increase in micronucleus frequency was observed in any of the tested stations compared to control (while in previous campaigns mutagenic activity was observed in some of the same stations), it can be assumed an interesting recovery from mutagenic pollution in the 2 last years. The samples were analysed for pH value, nitrogen, organic matter and carbonate content, and the concentration of some potentially mutagenic heavy metal ions (Zn, Cd, Ni, V, Cu) was assessed. In all samples, a concentration of heavy metals higher than unpolluted areas was observed. However, the alkaline pH measured should keep them as non-bioavailable elements.

Fabaceae↗

PubMed1992

The in vivo micronucleus test in human capillary blood lymphocytes: methodological studies and effect of ageing.

The in vivo micronucleus test in lymphocytes of human capillary blood collected by skin puncture is described. This method needs only 1-2 drops of finger blood. The normal value of micronucleus frequencies in lymphocytes from 250 healthy persons aged 6-88 years was determined. The upper limits of normal values were estimated by means of percentile. The 95th percentiles were 1/1000 and 1.5/1000 for the 6-45-year age group and the 46-88-year age group, respectively. There was no significant difference in micronucleus frequency between men and women. On the basis of micronucleus assays in more than 3000 cases, we consider that the micronucleus test in human capillary blood lymphocytes is a rapid, convenient and sensitive procedure for monitoring a human population exposed to environmental and occupational mutagens and carcinogens.

Adolescent↗

PubMed1989

In vivo micronucleus test using mouse hepatocytes.

The bone-marrow micronucleus (BMM) test is highly specific for clastogenic effects but its sensitivity is determined to a great extent by the substances tested, particularly by their metabolism. Some compounds, such as unstable mutagens or those which generate short-lived metabolites, are not detected in this test because the metabolites produced in the liver do not reach the bone marrow. In an attempt to provide qualitative and quantitative assessments of chromosomal mutations produced in vivo by genotoxic agents not detected in the mouse BMM test, a mouse-liver micronucleus test, adapted from Tates model, was developed. The animals were treated twice, with an interval of 24 h between treatments, and then subjected to partial hepatectomy (PH) 24 h after the second treatment in order to induce mitotic stimulation. The incidence of micronucleated hepatocytes was determined 96 h after PH. The test was evaluated with 5 procarcinogens, each with a complex metabolic pattern: dimethylnitrosamine (DMN), diethylnitrosamine (DEN), 1,1-dimethylhydrazine (1,1-DMH), 4-aminophenol (4-APOL), 4-aminobiphenyl (4-ABPYL) and one direct unstable mutagen, beta-propiolactone (BPL). All these compounds are negative in the mouse BMM test but caused a major increase in the incidence of micronuclei in mouse hepatocytes. This test is simple and can be readily compared with the BMM test. Furthermore, it offers a better assessment of the impact of a compound at the chromosomal level in a metabolically competent cell and can therefore be used for the evaluation of the genotoxic activity of compounds with complex metabolic pathways.

Aminobiphenyl Compounds↗

PubMedDate not supplied

The mouse peripheral blood micronucleus test with 2-acetylaminofluorene using the acridine orange supravital staining method.

The peripheral blood micronucleus test using the acridine orange (AO) supravital staining method was validated with the potent bone marrow clastogen 2-acetylaminofluorene (2-AAF). 2-AAF induced micronuclei in peripheral blood reticulocytes dose-dependently as well as in bone marrow polychromatic erythrocytes. The incidence of micronucleated reticulocytes (MNRETs) peaked 48 h after a single treatment in both CD-1 and BDF1 mice, and the incidence of micronucleated polychromatic erythrocytes (MNPCEs) peaked 24 or 48 h after treatment. The maximum incidences of MNRETs were always higher than those of MNPCEs in both mouse strains treated once. In the double-treatment regime, the maximum incidence of MNRETs was observed at 24 h after the second treatment in each strain. The incidences of MNRETs in BDF1 mice were higher than in CD-1 mice after a single treatment but were comparable after double treatment. These results indicate that the peripheral blood micronucleus test using AO supravital staining is as sensitive as the conventional bone marrow assay. The new staining method can be performed more easily than the original smear method using either bone marrow or peripheral blood cells. Thus, the peripheral blood method using AO supravital staining is a possible alternative to the conventional bone marrow assay.

2-Acetylaminofluorene↗

PubMed1989

Micronucleus test with benzo[a]pyrene using a single peroral administration and intraperitoneal injection in males of the MS/Ae and CD-1 mouse strains.

The effect of route of administration on the outcome of the micronucleus test was examined by administering benzo[a]pyrene (B[a]P) perorally (p.o.) and intraperitoneally (i.p.) to males of the MS/Ae and CD-1 mouse strains. This study consisted of 3 parts. First, an acute toxicity study lasting 3 days was done to estimate LD50s. The LD50 was larger than 1600 mg/kg for both routes in the 2 strains. Second, pilot micronucleus tests were carried out, on the basis of which an appropriate sampling time (48 h) and dose levels (62.5, 125, 250, and 500 mg/kg) were chosen for both routes and both strains. Third, full-scale micronucleus tests were done, which indicated that (1) B[a]P induced micronuclei dose-dependently by each administration route in each strain, (2) the i.p. route induced frequencies of micronuclei almost equal to or slightly higher than did the p.o. route, and (3) the MS/Ae strain was the higher responder.

Administration, Oral↗

PubMed1997

Species-specificity of pyrimethamine in the rodent bone marrow micronucleus test.

An antiprotozoal agent pyrimethamine is a potent clastogen that induces structural chromosome aberrations and micronuclei in cultured Chinese hamster (CHL) cells in vitro. Our previous study on the compound, however, demonstrated no significant induction of micronuclei in the mouse bone marrow micronucleus test, even with dosings on 4 consecutive days. In the present study, we investigated the clastogenicity of pyrimethamine in the rat bone marrow micronucleus test. An obvious dose-dependent increase in the frequency of micronucleated polychromatic erythrocytes (MNPCEs) was observed when the compound was given 3 times by oral gavage at 20-120 mg/kg/day. The MNPCE frequency at the highest dose was 80 times that of the control group. Single dose of pyrimethamine at 80 and 160 mg/kg also significantly induced MNPCEs. Thus, pyrimethamine showed species-specific effects in rodent bone marrow micronucleus assays. Our finding implies that micronucleus tests using not only mouse, but also rat, may be necessary for the evaluation of clastogens detected in in vitro cytogenetic studies.

Administration, Oral↗

PubMed1997

Evaluation of the rat bone marrow and peripheral blood micronucleus test using monocrotaline.

The present study was performed as part of the 9th collaborative trial of the CSGMT (Collaborative Study Group for the Micronucleus Test) to evaluate the performance of the rat micronucleus test in detection of clastogenic agents. Temporary fluorescent staining using acridine orange (AO) was compared with permanent staining using a modified Feulgen technique for bone marrow and Giemsa for blood. The Feulgen and AO methods were both found to be suitable for demonstrating micronucleus induction in rat bone marrow following oral administration of monocrotaline and cyclophosphamide. Induction of micronuclei was also shown using rat blood. The simple AO supravital method described produced uniformly stained preparations which were extremely easy to assess and interpret. The AO method was preferred to Giemsa for analysis of blood, but it was essential to analyse samples within 4 days of collection to avoid excessive deterioration of cells. Because of the relatively low number of micronucleated cells found in rat blood, it is suggested that examination of a larger number of cells may be necessary to achieve a similar sensitivity to the bone marrow assay for routine screening.

Acridine Orange↗

PubMed2001

Assessment of DNA damage in lymphocytes of workers exposed to X-radiation using the micronucleus test and the comet assay.

The mutagenic and carcinogenic effects of genotoxic agents on exposed people have constituted an increasing concern. Therefore, the objective of this work was to assess DNA damage in lymphocytes of workers exposed to X-radiation using the cytokinesis-blocked micronucleus test and the comet assay (single-cell gel electrophoresis), and to compare these two techniques in the monitoring of exposed populations. The cytokinesis-blocked micronucleus test and the comet assay were employed in the monitoring of 22 workers occupationally exposed to X-radiation in a hospital in southern Brazil. The frequency of dicentric bridges was also measured. The results of both assays and the frequency of dicentric bridges revealed a significant increase in genetic effects on the cells of exposed individuals. Age was significantly correlated with micronucleus frequency and damage index in the comet assay. The concomitant analysis of dicentric bridges when determining micronucleus frequency does not require much extra work, and may serve as a reference to the type of mutagenic effect (clastogenic or aneugenic). The combination of the alkaline comet assay with the cytokinesis-blocked micronucleus test appears to be very informative for the monitoring of populations chronically exposed to genotoxic agents.

Adult↗

PubMed1994

Induction of cytogenetic adaptive response of mouse bone marrow cells to radiation by therapeutic doses of bleomycin sulfate and actinomycin D as assayed by the micronucleus test.

An in vivo micronucleus assay using bone marrow cells of Syrian albino male mice for identifying the possibility of induction of adaptive response to various doses of radiation following treatment with chemotherapeutics is described. Single doses of bleomycin sulfate (BLM-S) at 300 micrograms/kg and actinomycin-D (ACT-D) at 10 micrograms/kg body weight (therapeutic dose range) were injected intravenously 3 h prior to whole body gamma-irradiation. Irradiation at various doses from 1-4 Gy was carried out at a dose rate of 45 cGy/min. Animals were killed at 24, 36 and 48 h post-irradiation. The results obtained in this study clearly indicate a significant difference for radiation induced micronuclei (MN) in polychromatic erythrocytes (PCEs) with P value < 0.001 over the dose range used. When used in combination with radiation, neither ACT-D nor BLM-S caused a synergistic or additive effect. Irradiated animals showed a higher incidence of micronuclei formation in the presence of ACT-D and BLM-S. However, in both cases, the number of MN induced in PCEs was less than the sum of MN induced by radiation and ACT-D or BLM-S alone. The effect of combined treatment was reduced by a factor of 1.5 for BLM-S and greater than 1.5 for ACT-D treated animals. These observations indicate that although a small amount of ACT-D or BLM-S reaches the bone marrow cells via the circulation, these drugs might produce effects which make bone marrow cells resistant to the clastogenic effects of radiation. Therefore, using these agents repeatedly for cancer treatment in combination with radiation might not cause severe adverse biological effects in normal hemopoeitic tissue.

Animals↗

PubMed1984

Genotoxic effects of dioxolane and trioxane in mice evaluated by the micronucleus test.

The possible genotoxic effects of dioxolane and trioxane were studied using the micronucleus test. Mice were given dioxolane and trioxane i.p. in two doses at 24-h intervals. Dioxolane at doses from 1500 mg/kg to 6000 mg/kg caused a significant increase of micronucleated polychromatic erythrocytes in bone marrow of mice as compared to the negative control value. Positive results in the micronucleus test provide evidence of genotoxic activity of dioxolane. I.p. administration of trioxane produced no chromosomal damage resulting in erythrocyte micronucleus formation, even at highly toxic doses.

Animals↗