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At least 19 recordsLinked to original sources
PubMed1979

Mutagenic evaluation of nitroparaffins in the Salmonella typhimurium/mammalian-microsome test and the micronucleus test.

Three nitroparaffins (nitroethane, 1-nitropropane, and 2-nitropropane) were studied in the Salmonella typhimurium/mammalian microsome (Ames) test, with and without microsomal activation systems. Nitroethane and 2-nitropropane also were studied in an in vivo mutagenic (micronucleus) test. These studies were undertaken because these solvents are widely used in the chemical and pharmaceutical industries and 2-nitropropane was reported to cause liver cancer in rats exposed by the inhalation route. Neither nitroethane nor 1-nitropropane was active in the Ames test with Salmonella tester-strains TA1537, TA92, TA98, or TA100. However, 2-nitropropane produced a significant increase in revertants in all of these tester strains, particularly strain TA100, where 3 microliter/plate doubled the number of revertants in the presence of microsomal enzymes. Negative results were obtained with both nitroethane and 2-nitropropane in micronucleus tests. These studies have shown that 2-nitropropane has the potential for causing point mutations in a microbial test system. However, this compound probably will not cause a chromosome mutation of the clastogenic type.

Alkanes↗
PubMedDate not supplied

Micronucleus test with mouse peripheral blood erythrocytes by acridine orange supravital staining: the summary report of the 5th collaborative study by CSGMT/JEMS.MMS. The Collaborative Study Group for the Micronucleus Test.

The main goal of the Collaborative Study Group for the Micronucleus Test (CSGMT) was to validate a new method for the micronucleus test, recently introduced by Hayashi et al. (1990), using mouse peripheral blood cells stained supravitally with acridine orange (AO). The micronucleus tests were performed on CD-1 mice using 23 chemicals with various modes of action. As a rule, one chemical was studied by two participants. Peripheral blood sampled from the same animal was examined 0, 24, 48, and 72 h (or longer) after treatment. The frequencies of micronucleated peripheral reticulocytes (MNRETs) were recorded based on observation of 1000 reticulocytes per mouse. All chemicals induced MNRETs dose-dependently. Interlaboratory differences in the induction of MNRETs were in an acceptable range for most chemicals tested. Although differences were observed with some chemicals, there were no discrepancies in qualitative judgment. Most chemicals gave the greatest response 48 h after treatment, which was less variable than in the bone marrow assay (greatest response, 24-48 h). These results suggest that the peripheral blood assay using the AO supravital staining technique generates reproducible and reliable data to evaluate the clastogenicity of chemicals. This makes the peripheral blood micronucleus assay an attractive alternative to the conventional bone marrow assay.

Acridine Orange↗
PubMed1989

Genotoxicity of air pollution in a non-ferrous metal foundry in three bacterial tests and a micronucleus test--a comparative study.

Acetone extracts of dusts and fumes collected at workplaces in a non-ferrous metal foundry exhibited genotoxic activity in all of the tests used. Of the compared tests, the Ames method is the most useful for preliminary screening detection of the genotoxic agents that are present in acetone extracts of dusts and fumes emitted at workplaces in a non-ferrous metal foundry.

Air Pollutants, Occupational↗
PubMedDate not supplied

Single versus multiple dosing in the micronucleus test: the summary of the fourth collaborative study by CSGMT/JEMS.MMS. Collaborative Study Group for the Micronucleus Test, the Mammalian Mutagenesis Study Group of the Environmental Mutagen Society, Japan (CSGMT/JEMS.MMS).

The effects of multiple dosing in the micronucleus test were studied by treating male CD-1 mice 1, 2, and 4 times i.p. with various doses of 11 chemicals and by sampling bone marrow cells 6, 24, 48, and/or 72 h after the final dosing. The chemicals used were 2-acetylaminofluorene (2-AAF), 1-beta-D-arabinofuranosylcytosine (ARA-C), 7,12-dimethylbenz[a]anthracene (DMBA), ethyl methanesulfonate (EMS), N-ethyl-N-nitrosourea (ENU), 6-mercaptopurine (6-MP), phenacetin (PHEN), 5-fluorouracil (5-FU), methotrexate (MTX), benzene (BEN), and potassium chromate (K2CrO4). MTX, an inhibitor of nucleotide synthesis, was a weak micronucleus inducer after single dosing, but clearly positive after multiple dosing. Although ARA-C, 5-FU, and 6-MP became positive after single dosing, the multiple dosing enhanced the effects of these base analogues. ENU, DMBA, and BEN, at some doses and sampling times, also showed increased responses by multiple dosing, but a severe trade-off occurred enhanced toxicity tended to reduce the bone marrow cells, especially at 4 dosings, making the examination of micronuclei difficult. PHEN showed the multiple-dosing effect after 2 doses, but the effect disappeared at quadruple dosing. No apparent multiple-dosing effects were observed with 2-AAF, EMS, and K2CrO4, which gave similar incidences of micronuclei after single and double dosing. The original double dosing and sampling 6 h after the second injection method of Schmid (1975) was less sensitive than the modified method, i.e., sampling 24 h after the second dosing. The latter regimen is recommended for the general screening for the following reasons. (1) It was the most sensitive protocol among those tested here and detected all test chemicals as clastogens. (2) Since bone marrow specimens were prepared at or near the steady state of micronuclei, one sampling covered most chemicals with different actions. (3) For chemicals having multiple-dosing effects the recommended regimen was better than the protocol using 4 doses, because specimens could be prepared before the suppression of the bone marrow became excessive. (4) Chemicals having no multiple-dosing effect showed similar incidences of micronuclei after single and double dosing. (5) Dose selection is easier than with more multiple dosing, because, e.g., 50, 25, and 12.5% of LD50 values determined on single dosing will usually be tolerated by test animals. The detection spectrum would become wider if specimens are also prepared 48 h after the second dosing for metabolic inhibitors, base analogues, and the other chemicals which might show delayed activities.

Animals↗
PubMed1991

Investigation of soy sauce treated with nitrite in the chromosomal aberration test in vitro and the micronucleus test in vivo.

Soy sauce pretreated with 2300 ppm nitrite caused no more aberrations than did untreated soy sauce in the chromosomal aberration test in vitro using a Chinese hamster fibroblast cell line with or without S9 mixture. The aberration induction by soy sauce is likely to be caused by the 17% sodium chloride it contains. Soy sauce with or without pretreatment with 2300 ppm nitrite was orally given to ICR mice at a dose of 14 ml/kg body weight once or 6 ml/kg body weight/day for 5 consecutive days. This oral administration did not induce any significant increase in micronuclei in the micronucleus test in vivo.

Animals↗
PubMed1979

Mutagenicity tests of diflubenzuron in the micronucleus test in mice, the L5178Y mouse lymphoma forward mutation assay, and the Ames Salmonella reverse mutation test.

Diflubenzuron, one of a new class of pesticides believed to act via inhibition of chitin synthesis in the developing insect cuticle, was tested for possible mutagenic activity using the micronucleus test in mice, the L5178Y mouse lymphoma forward mutation test at the thymidine kinase locus, and the Ames Salmonella/microsome reverse mutation test. No mutagenic effect was found.

Animals↗
PubMed1992

Sampling times in micronucleus testing.

A series of micronucleus inducers were evaluated in the mouse bone marrow micronucleus test to determine if a 72-h sampling time enhances the sensitivity for detecting genotoxic agents. Male and female Swiss albino mice were dosed once with 7,12- dimethylbenz[a]anthracene, 6-mercaptopurine, benzo[a]pyrene, benzene, cyclophosphamide, 2-acetylaminofluorene, tubulazole, or mitomycin C. According to the EEC and OECD guidelines, the mice were killed at 24, 48 and 72 h after dosing. All test compounds induced an increase in the number of micronucleated polychromatic erythrocytes at 24 and/or 48 h. From the results obtained, it was evident that the 72-h sampling time does not enhance the sensitivity of the micronucleus test. The present data show that for screening purposes two sampling times at 24 and 48 h are sufficient to detect clastogens as well as aneugens. Although quantitative differences were found in sensitivity to micronucleus inducers between male and female mice, no qualitative differences were observed between the two sexes.

Animals↗
PubMed1990

[Assessment of the mutagenic effect of maternal factors on human chorionic villi by micronucleus test].

Rapid determination of DNA damage by micronucleus test is well accepted. Animal bone marrow cells or human peripheral lymphocytes used in most studies could not directly reflect the influence of the mutagenic effect on the offsprings by environmental factors. Human chorionic villi micronucleus test to detect directly the mutagenic effect of environmental factors has not been reported in the literature. Direct determination of human chorionic villi micronuclei (CVMN) was established in our laboratory, to study the mutagenic effect of mother's age, gravidity, gestation age, abortion history, contraception (condom, diaphragm, rhythm, oral contraceptives, spermicide or IUD), smoking and drinking on the offsprings. Cross investigation and micronucleus test were used in 507 couples undergoing artificial abortion. Micronuclei were scored according to Countryman's standard 2,000 interphases were observed in each subject for CVMN frequency (%). Arcsine transformation (arcsine [Sqr (P)]) was used in transforming CVMN frequency and the analysis of variance were used for statistics. No correlation between CVMN frequency and mother's age, gravidity, gestation age, abortion history, and contraception was found. Neither smoking nor drinking habit was found among the women of this study. The CVMN frequency of husband smoking was 0.7645 +/- 0.0561%, of husband non-smoking-drinking was 0.5522 +/- 0.0616%, of husband drinking was 0.5667 +/- 0.2004%, of husband smoking and drinking was 0.7944 +/- 0.0754%. There was a statistical difference in CVMN frequency between husband smoking and non-smoking (F = 2.78 DF = 408 P less than 0.05). No significant difference was found between husband drinking and non-drinking.

Alcohol Drinking↗
PubMed1977

Cytogenetic findings in pernicious anaemia. Comparison between results obtained with chromosome studies and the micronucleus test.

To elucidate whether the micronucleus test may be a sensitive test for the demonstration of the occurrence of spontaneous structural chromosomal aberrations in human disease, bone-marrow smears and chromosome preparations were studied from ten patients with pernicious anaemia. An increased incidence of metaphases with structural chromosomal aberrations was seen in three of the patients, whereas an increased number of bone-marrow cells containing micro-nuclei was present in eight of the ten patients. The micronucleus test may thus be a rapid and sensitive test to demonstrate whether spontaneous structural aberrations of the chromosomes are present in a group of patients suffering from various diseases.

Adult↗
PubMed1991

Evaluation of the in vivo genotoxicity of the structural analogues 2,6-diaminotoluene and 2,4-diaminotoluene using the rat micronucleus test and rat liver UDS assay.

The two structural isomers 2,4- and 2,6-diaminotoluene (DAT) differ in their carcinogenic properties; the 2,4-isomer is carcinogenic in rats and mice, whereas the 2,6-isomer has been reported to be non-carcinogenic. Both isomers were reported to be mutagenic in Salmonella typhimurium in the presence of S9, which was confirmed in the present study before in vivo assays were commenced. Both isomers were tested in the rat bone marrow micronucleus test and the rat liver UDS test to investigate how well these assays discriminate between the carcinogenic and the non-carcinogenic isomer. In the micronucleus test both isomers gave weakly positive results; however, with the carcinogen 2,4-DAT this weak effect was only detectable at very toxic doses and therefore the biological relevance of this result is questionable. Thus, the micronucleus test did not discriminate correctly between the carcinogen and the non-carcinogen. With the liver UDS test, discrimination was achieved but the positive effect seen for the carcinogenic isomer was weak and dependent on the method of preparation of the dosing suspensions. The results are discussed in relation to the carcinogenicity data on both compounds. It is concluded that although both isomers are potent genotoxins in vitro they exert their genotoxic potential only weakly in vivo and convincing discrimination between the carcinogenic and non-carcinogenic isomer was not demonstrated.

Animals↗
PubMed1989

The mouse bone marrow micronucleus test: evaluation of 21 drug candidates.

The mouse bone-marrow micronucleus test is one of the most widely used genetic toxicology assays. In this report the results of testing 21 compounds in the micronucleus test are presented. Of the 21 compounds tested, 3 potential chemotherapeutic agents were identified as strongly clastogenic. In addition, one compound was identified as a weak inducer of micronuclei in the assay. Further testing of this compound in an in vivo bone marrow metaphase analysis failed to confirm this material as clastogenic. The remaining 17 compounds were classified as negative in the assay. In general the results of the micronucleus test agreed with the results of other genetic toxicology assays on this group of compounds.

Animals↗
PubMedDate not supplied

Mutagenicity studies on irradiated potatoes and chlorogenic acid; micronucleus test in rats.

The micronucleus test was used to study possible mutagenic effects of (1) Irradiated potatoes extracted (a) immediately and (b) after 24-h storage following irradiation; (2) Irradiated and unirradiated chlorogenic acid; and (3) Trenimon. It was observed that irradiated potatoes (groups 1 a, b) and chlorogenic acid (group 2) did not cause mutagenic effects in the bone-marrow cells of rats. The Trenimon group (group 3), which was used as the positive control group, did show significant mutagenic effects.

Animals↗
PubMed1992

Detection of micronuclei after exposure to mitomycin C, cyclophosphamide and diethylnitrosamine by the in vivo micronucleus test in mouse splenocytes.

A micronucleus detection test using mouse splenocytes has been adapted from a method previously carried out using human lymphocytes. An ex vivo protocol was chosen: male C57B16 mice were treated with various compounds. Splenocytes were then isolated and placed in culture for 48 h and stimulated with concanavalin A and conditioned medium. The cytokinesis-block method reported by Fenech and Morley was used to detect and score micronuclei in the proliferating lymphocytes (3 micrograms/ml of cytochalasin B for 16 h). Three mutagenic clastogens, mitomycin C (MMC), a direct alkylating agent (0.4, 0.8 and 1.6 mg/kg), cyclophosphamide (CP), an indirect alkylating agent (25, 50 and 100 mg/kg) and diethylnitrosamine (DEN), an indirect alkylating agent with labile metabolites (25, 50 and 100 mg/kg), were tested at four sampling times (2, 4, 8 and 15 days). All three compounds were detected from 48 h after treatment. This method was indeed able to detect clastogenic compounds normally detected by the mouse bone marrow micronucleus test (MMC, CP) as well as a compound with labile metabolites which is not usually detected by this test (DEN). Maximum micronucleus induction was observed after 4 days for MMC, 2 days for CP and 15 days for DEN. This method thus appears to offer a potentially useful toxicological test for assessing in vivo clastogenicity.

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↗
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↗
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↗