PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Micronucleus Tests”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources
PubMed1994

Validation of the in vivo CD1 mouse splenocyte micronucleus test.

In order to validate the in vivo micronucleus test in mouse splenocytes using the cytokinesis block method, 14 compounds with various mechanisms of action were tested: three direct alkylating agents (mitomycin C, ethylnitrosourea, beta-propiolactone), seven indirect alkylating agents (cyclophosphamide, benzo[a]pyrene, diethylnitrosamine, dimethylnitrosamine, 4-aminophenol, 4-aminobiphenyl, 1,1-dimethylhydrazine), two intercalating agents (acridine orange, ethidium bromide) and two spindle poisons (vincristine, colchicine). Male mice were dosed once with the compound, and spleen samples were taken 2 or 14 days after treatment. A significant increase in the binucleated micronucleated splenocyte rate was observed with all the alkylating and intercalating agents at at least one sampling time. In contrast, no increase in the binucleated micronucleated splenocyte rate was observed with the spindle poisons. In conclusion, under these experimental conditions, this in vivo test seems appropriate for the detection of clastogenic compounds including compounds that cannot be detected in the bone marrow micronucleus test. The limit of this test, as expected, is the lack of detection of aneugenic compounds.

Alkylating Agents↗
PubMed1989

Administration-route-related differences in the micronucleus test with benzene.

The effect of route of administration on the outcome of the micronucleus test was studied in 2 laboratories by administering the model chemical benzene intraperitoneally (i.p.) and orally (p.o.) to 2 strains of mice: MS/Ae and CD-1. On the basis of results obtained in a small-scale acute toxicity study and in a pilot micronucleus test, full-scale micronucleus tests were performed with a 24-h sampling time at doses of 250, 500, 1000, and 2000 mg/kg i.p. and 500, 1000, 2000, and 4000 mg/kg p.o. In both strains of mice, a higher incidence of micronucleated polychromatic erythrocytes (MNPCEs) was observed after p.o. administration. The ratio of polychromatic erythrocytes (PCEs) to total erythrocytes decreased more markedly at higher doses i.p. in both strains. Thus, benzene induced more micronuclei via the p.o. route, while inhibitory effects on bone marrow cells were stronger after i.p. administration.

Administration, Oral↗
PubMed2004

2-Hydroxy-1,4-naphthoquinone, the natural dye of Henna, is non-genotoxic in the mouse bone marrow micronucleus test and does not produce oxidative DNA damage in Chinese hamster ovary cells.

2-Hydroxy-1,4-naphthoquinone (HNQ) has been found positive in a previous chromosome aberration test in Chinese hamster ovary (CHO) cells and in a mouse bone marrow micronucleus test at 72h after oral administration (vehicle: DMSO). However it was negative at 24 and 48h sampling times, and in subsequent micronucleus tests that used 0.5% aqueous methyl cellulose (MC) as vehicle. We performed a bone marrow micronucleus test in male and female NMRI BRL/BR mice at oral doses of 75, 150 and 300mg/kg in two vehicles (DMSO and 0.5% aqueous MC), evaluated micronuclei at 24, 48 and 72h, plasma levels of HNQ at 0.5, 1 and 4h, and haematology parameters at 72h after administration. The mechanism of in vitro clastogenic activity of HNQ was investigated by evaluation of the potential of HNQ to produce oxidative DNA damage after treatment of CHO with 10mM HNQ, followed by quantification of DNA fragments using the comet assay. In the micronucleus test, HNQ at 300mg/kg produced mortality and clinical signs at similar incidence and severity for both vehicles. Levels of HNQ in the plasma of treated mice were dose-related, of similar magnitude for both vehicles, but higher in females than in males. Maximum concentrations were found at 0.5 or 1h. At 300mg/kg, HNQ slightly affected RBC parameters suggesting haematotoxicity. No increase in the frequency of micronuclei was observed for any dose, vehicle or time point, whereas the positive control substance (CPA) produced a clear positive response. No evidence of HNQ-induced oxidative DNA damage was found at clastogenic concentrations in vitro, whereas the positive control substance (H(2)O(2)) produced a clear increase. In conclusion, HNQ was negative for induction of bone marrow micronuclei in mice up to 72h after administration in two different vehicles, and its in vitro clastogenicity was not due to oxidative damage. These results confirm that HNQ poses no or negligible genotoxic risk.

Animals↗
PubMed1981

Micronucleus test and bone-marrow chromosome analysis: a comparison of 2 methods in vivo for evaluating chemically induced chromosomal alterations.

The sensitivities of 2 cytogenetic tests, chromosome analysis and the micronucleus test, were compared by using mice exposed to the substances methyl methanesulfonate (MMS), mitomycin C (MC) and procarbazine (Natulan). The lowest dose at which a significant effect could be observed in bone-marrow cells of mice was determined. Both test systems proved equally sensitive for MC and procarbazine. Doses as low as 0.16 mg of MC per kg and 3.12 mg of Natulan per kg significantly increased both the aberration rates and the micronucleus rates above those of the controls. In contrast, after exposure to MMS, chromosomal aberrations were elevated above control levels at 5 mg/kg, and the micronucleus rate differed significantly from that of the controls after a dose of 10 mg/kg. With the present protocol and sample size one can conclude that the micronucleus test is generally comparable in sensitivity to the chromosome analysis. However, the MMS data indicate that there might be chemicals for which the resolution of the chromosome analysis is higher. When the mutagens were given in 2 single i.p. injections separated by 24 h, the polychromatic erythrocytes were analyzed for the presence of micronuclei 6 or 24 h after the second injection. The double treatment did not increase the micronucleus rates above the single-treatment results at either sampling interval.

Animals↗
PubMed2002

Collaborative validation study of the in vivo micronucleus test using mouse colonic epithelial cells.

The in vivo micronucleus test using mouse colonic epithelial cells was evaluated as the 11th collaborative study organized by the Collaborative Study Group on the micronucleus test (CSGMT) with three model chemicals that were known to induce chromosome damage in mouse colonic cells. Five laboratories participated in this validation study. All three model chemicals, i.e. 1,2-dimethylhydrazine dihydrochloride (1,2-DMH), N-methyl-N-nitrosourea (MNU), and mitomycin C (MMC), induced micronucleated colonic epithelial cells in a 4-day exposure protocol in all participating laboratories. We confirmed that the present single cell suspension method could be used to detect the model chemicals as micronucleus inducers in mouse colonic epithelial cells. Advantages of this method are that experiments are easy to perform and that intact cells can be analyzed. The present study suggested that the colon micronucleus assay proposed here is useful for mechanistic studies of colon carcinogenesis.

1,2-Dimethylhydrazine↗
PubMed1993

Micronucleus test and erythropoiesis: effect of cobalt on the induction of micronuclei by mutagens.

The micronucleus test is used widely as an in vivo short-term assay for potential carcinogens. In the present study, results of the micronucleus test were affected by cobalt dichloride pretreatment. Cobalt dichloride was used to induce erythropoietin, a growth factor for erythropoiesis. The increase in mutagen-induced micronucleus response following cobalt pretreatment, therefore, may have been due to a change in the rate of erythropoiesis. The greatest interaction between cobalt pretreatment and mutagen treatment for the induction of micronucleated polychromatic erythrocytes (MPCE) occurred when mice were injected with 1,1-dimethylhydrazine (DMH) 12-24 hr after pretreatment with cobalt dichloride and killed 30 hr later. Increased sensitivity of the micronucleus test was attributable to the administration of mutagen during the differentiation and multiplication of erythroblast, which is presumed to have been accelerated by pretreatment with cobalt dichloride. An increased induction of MPCE in the bone marrow by two chemicals--benzo(a)pyrene, 2-naphthylamine--was also observed following pretreatment with cobalt dichloride.

2-Naphthylamine↗
PubMed1989

Administration-route-related differences in the micronucleus test with N-ethyl-N-nitrosourea.

Administration-route-related differences in the micronucleus test were examined by giving N-ethyl-N-nitrosourea (ENU) to male mice of the MS/Ae and CD-1 strains by 2 different routes, intraperitoneally (i.p.) and orally (p.o.). The experiments consisted of 3 parts: (1) a simplified acute toxicity study, which gave LD50s of 490 (i.p.) and 840 mg/kg (p.o.) in MS/Ae and 640 (i.p.) and 960 mg/kg (p.o.) in CD-1 mice: (2) a pilot experiment for the full-scale micronucleus test to determine appropriate dosages and sampling time: and (3) the micronucleus test at doses of 12.5, 25, 50, and 100 mg/kg with a sampling time of 24 h. The results indicated that no route-related differences existed at the 2 lowest doses. At 50 mg/kg, markedly higher numbers of micronucleated polychromatic erythrocytes (MNPCEs) were induced in both mouse strains by the i.p. route. At 100 mg/kg, the difference between the routes decreased in strain CD-1 and even reversed in MS/Ae. Thus, route-related differences appeared to depend on the dose. Such differences became small, however, in both strains when the comparison was made on the basis of LD50 values.

Administration, Oral↗
PubMedDate not supplied

[Genotoxic effects of pesticide-treated vegetable extracts using the Allium cepa chromosome aberration and micronucleus tests].

The presence of chemical residues in vegetables and fruit is a source of human exposure to toxic and genotoxic chemicals. The mutagenic and carcinogenic action of herbicides, insecticides and fungicides on experimental animals is already known. Several studies have shown that chronic exposure to low levels of pesticides can cause adverse health effects and that many pesticides are mutagenic/carcinogenic. In the present research we monitored concurrently the presence of pesticides and genotoxic compounds extracted from 21 treated vegetables and 8 types of grapes sampled from the markets of a region in Southern Italy. The extracts were analysed for pesticides by gas-chromatography and HPLC, and for genotoxicity with two plant tests in Allium cepa roots: the micronucleus test and the chromosomal aberration test. We found 33 pesticides, some of which are outlawed. Genotoxicity was found in some of the vegetables and grapes tested. Allium cepa tests were sensitive for monitoring genotoxicity in food extracts. The micronucleus test in interphase cells gave much higher mutagenicity than the chromosomal aberration test in anaphase-telophase cells.

Allium↗
PubMed1993

The in vitro micronucleus test on isolated human lymphocytes.

The in vitro micronucleus test was performed on isolated human lymphocytes using the cytokinesis-block technique with and without a rat liver metabolizing system. Positive control substances were used to evaluate this test: a direct agent (vincristine) requiring no metabolic activation, and three promutagens (cyclophosphamide, benzo[a]pyrene and dimethylbenz[a]anthracene). All of them, when compared with controls, caused a significant increase in micronucleus frequency, with a clear dose response. Five compounds were then tested in this in vitro micronucleus test: safrole, azathioprine, procarbazine, diethylstilbestrol and o-toluidine. The chemicals were examined with and without exogenous metabolic activation. Of these five compound, o-toluidine was found to be a marked direct genotoxic agent and azathioprine gave positive results with or without metabolic activation (a better response was noted without the addition of S9 mix). Diethylstilbestrol gave conflicting results and was considered inconclusive. Two chemicals, safrole and procarbazine, were found to be non-genotoxic in this test system, whatever the protocol used.

Adult↗
PubMed1986

[Micronucleus test in cultured cells--preliminary study].

In mutagenicity and carcinogenicity assays using micronucleus test, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), 50 mg/kg or benzo(a)pyrene (BaP), 100 mg/kg did not increase the incidence of micronuclei in polychromatic erythrocytes in bone marrow of mice. MNNG, 0.1 microgram/ml could induce a significant increase of micronuclei with dose response in cultured V79 cells. In another experiment of Syrian hamster embryo cells, the induction of micronuclei was seen after benzo(a)pyrene, 0.1 microgram/ml treatment. The combined use of micronucleus test in vivo and in vitro can increase the sensitivity and reduce the false negativity obtained in vivo micronucleus test.

Animals↗
PubMed1989

The micronucleus test in Xenopus: a new and simple 'in vivo' technique for detection of mutagens in fresh water.

The aim of this study was to extend the micronucleus test to Xenopus laevis to screen water for potential mutagens. Up to now, the most commonly used methods for screening fresh water are the bacterial tests (Ames tests). Ames tests are well validated, but are merely in vitro bacterial assays which can only detect point mutations whereas the micronucleus test is an in vivo assay using a vertebrate species, and thus is able to detect both chromosome and genome mutations. This study was designed to optimize the micronucleus test for Xenopus. Three different variables were investigated: (i) the effect of temperature; (ii) the effect of the stage of larval development; and (iii) the effect of varying or continuous exposure concentrations. In addition, a dose-response curve was established for eight concentrations of benzo[alpha]pyrene. The results indicate that the micronucleus test with Xenopus can be used to monitor water pollution.

Animals↗
PubMed1990

[Use of cytochalasin B in the micronucleus test in human peripheral lymphocytes].

The micronucleus test is one of the alternative procedures of cytogenetic analysis. Its modification with the use of cytochalasine B (Calbiochem AG) ensures safely the recording of changes of the genetic apparatus in the first cellular cycle after an attack of a mutagenic agent on human peripheral lymphocytes. The authors elaborated a reproducible modification of the original work of Fenech and Morley--published in this country by Kocisová and Srám--and describe in detail its individual steps. The cytochalasine MN-test which should become part of obligatory standard procedures of Czechoslovak preventive health services (formerly hygiene service) is thus open to confirmation.

Cytochalasin B↗
PubMed1989

Administration-route-related difference in the micronucleus test with 7,12-dimethylbenz[a]anthracene.

The effect of route of administration on the outcome of the mouse micronucleus test was evaluated in 2 laboratories by administering a model chemical, 7,12-dimethylbenz[a]anthracene (DMBA) by intraperitoneal injection (i.p.) and oral gavage administration (p.o.) to males of 2 mouse strains, MS/Ae and CD-1. On the basis of a small-scale acute toxicity study and a pilot micronucleus test, a full-scale micronucleus test was performed with a 48-h sampling time at doses of 25, 50, 100, and 200 mg/kg by both administration routes in the 2 strains. At each dose level and in both strains, higher frequencies of micronucleated polychromatic erythrocytes (MNPCEs) were found after use of the i.p. route. In the MS/Ae strain, a linear, positive dose response was obtained by both routes. In the CD-1 strain, the maximum response was reached at 100 mg/kg and a downturn occurred at 200 mg/kg by both routes. The comparison of maximum responses indicated that MS/Ae was the higher responder for both routes of application. Although DMBA induced micronuclei more efficiently by the i.p. route than after oral administration on a mg/kg base, this route-related difference was reversed in both strains when the comparison was made on the basis of LD50 values and when the maximum responses were neglected.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1993

In vivo detection of waste water and industrial effluent genotoxicity: use of the Newt Micronucleus Test (Jaylet Test).

The genotoxic potential of various waste waters has been evaluated in a micronucleus test using amphibian larvae. Genotoxicity was detected after dilution, in waste water from tanneries and from various petrochemical industries. Further studies have shown that sample treatment used for in vitro testing may affect the genotoxic response. Sterilization by gamma irradiation lowered genotoxic activity. Furthermore, microfiltration of effluent and extraction of organic micropollutants on XAD-4 resins, lead to the preparation of extracts which are not fully representative of the initial water sample. Testing of concentrates, as required for in vitro studies, will limit the scope of a survey to that part of the organic matter that can be recovered by concentration techniques. Many of the problems encountered in in vitro genotoxicity studies of waters, may be circumvented with direct testing on aquatic organisms. Thus, there is no need to concentrate or sterilise a sample. The tests can be carried out with intact animals, thus taking into account uptake and elimination, internal transport and metabolism. Finally, in vivo test-systems, such as the Newt Micronucleus Test, are more relevant to eukaryotes than bacterial assays and are suitable to assess the real impact of genotoxins discharged in the aquatic environment.

Animals↗
PubMed1990

Micronucleus test of mofezolac (N-22).

A micronucleus test using BDF1 male mice was conducted in order to evaluate the in vivo mutagenicity of mofezolac (N-22). N-22 was orally administered at doses of 75, 150, 300 and 600 mg/kg, with a sampling time of 24 hr. The frequency of polychromatic erythrocytes with micronuclei was 0.07-0.08% in the groups treated with N-22 and did not differ markedly from that of the vehicle control (0.13%). The present study indicates that N-22 has no in vivo mutagenic properties.

Animals↗
PubMed1997

Genotoxicity of nitro musks in the micronucleus test with human lymphocytes in vitro and the human hepatoma cell line Hep G2.

The nitro musk compounds musk xylene (1-tert.-butyl-3,5-dimethyl-2,4,6-trinitrobenzene), musk ketone (4-tert.-butyl-3,5-dinitro-2,6-dimethylacetophenone), musk ambrette (1-tert.-butyl-4-methyl-6-methoxy-3,5-dinitrobenzene), musk moskene (1,1,3,3,5-pentamethyl-4,6-dinitroindane) and musk tibetene (1-tert.-butyl-3,4,5-trimethyl-2,6-dinitrobenzene) were tested for their genotoxic activity in the micronucleus test (MN) with human lymphocytes in vitro and the human hepatoma cell line Hep G2. Compound concentrations were employed up to cytotoxic doses. Musk xylene, musk ketone, musk ambrette, musk moskene and musk tibetene revealed no genotoxicity in the micronucleus test with human lymphocytes and with the human hepatoma cell line Hep G2.

Adult↗
PubMed1992

Evaluation of the micronucleus test using a Chinese hamster cell line as an alternative to the conventional in vitro chromosomal aberration test.

The in vitro micronucleus (MN) test was carried out simultaneously with the conventional chromosomal aberration (CA) test on 11 clastogenic chemicals or spindle poisons with different modes of action using a Chinese hamster cell line (CHL). The method of slide preparation for the MN test was the same as that for the conventional metaphase analysis, except that 1% acetic acid in methanol was used as the cell suspension medium for air-drying (to preserve the cytoplasm around the nucleus). All chemicals tested induced micronuclei reproducibly and dose-dependently in good agreement with the results of metaphase analysis (r = 0.99). Since the MN test methodology is simple and the observation of MN is less subjective than that of CA, we conclude that the in vitro MN test would be a good alternative to the conventional CA test for screening the genotoxicity of chemicals.

Acetates↗