SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
4 important flavonoid compounds, namely quercetin, kaempferol, neohesperidin dihydrochalcone and rutin, were administered to male mice for the detection of gross chromosomal anomalies by the micronucleus test. The first 3 compounds were positively clastogenic to different extents, whereas the 4th was negative.
A pilot experiment was undertaken to find the optimal dose range and sampling time in the micronucleus test; 2 animals per group were used. The chemical was injected at 4 different doses, and smear preparations were made from femoral marrow cells at 5 different sampling times for each dose group. The incidence of micronucleated polychromatic erythrocytes was scored on the preparations stained with acridine orange. When the data were arranged two-dimensionally, the optimal dose and sampling time which could be used for a further full-scale test, could be estimated. In addition, sex differences and the effect of multiple treatment can be estimated using this protocol with minor modifications.
The mutagenic potential of ortho-phenylenediamine--known by studies on Salmonella typhimurium--was studied in mice, Chinese hamsters and Guinea pigs with the use of the micronucleus test. In bone marrow of all three species, chromosomal damage was detected following intraperitoneal injections of the test chemical, this damage was seen also after peroral administration to mice. Four derivatives of ortho-phenylenediamine containing one or two methyl-, nitro- or chlorosubstituents in 4- or 5-position of the aromatic ring were studied in mice. Of these the 4-methyl-derivative induced micronuclei, the 4-nitro-, 4,5-dimethyl-, and 4,5-dichloroderivatives were inactive. The results indicate that the chemical nature and the number of substituents influence the chromosome damaging potential.
Sediments collected in Tiber river and in its main tributary water courses within the urban area of Rome were tested for mutagenicity by means of Vicia faba root tips micronucleus (MN) test. Representative samples were scored for micronucleus generating events (chromosome/chromatid loss and fragments) too. Sediments were assayed for content of the thirteen most important chemicals of polycyclic aromatic hydrocarbon (PAH) group and for some heavy metal ions (Cd, Cr, Cu, Ni, Pb, Zn). Samples were collected in four tributary rivers (Prima Porta, Acqua Traversa, Aniene and Magliana) just before their confluence with Tiber river and at different stations along the Tiber river itself upstream and downstream the sites of confluence of the sampled tributaries. All samples were collected in July 1992. An alarming level of mutagenicity was reached in most of the tested stations, with an effect comparable to an X-rays exposure up to 0.4 Gy. Chemical analysis showed that the total amount of identified PAHs ranged from 4.5 to 625.2 ng/g of dry matrix in the different stations and the total amount of heavy metals ranged from 130 to 570 ppm. Tiber mutagenicity is likely to be mainly due to local factors such as the confluence of a small polluted tributary rather than to large scale effect due to an upstream-downstream relationship.
2 dialkylnitrosamines, 4 oxazaphosphorines, 6 aryldialkyltriazenes, urethane, N-hydroxyurethane, 4-nitroquinoline-1-oxide, procarbazine (natulan) and the inorganic carcinogen potassium chromate were studied for cytogenetic activity in the micronucleus test on mouse bone marrow. Except diethylnitrosamine, all chemicals were active. The results are compared with those known from studies in other mammalian and sub-mammalian test systems. The results of the micro nucleus test correlate well with results from other mutagenicity tests and with the carcinogenicity of the chemicals. The lack of an effect on N-nitrosodiethylamine (DENA) is discussed with regard to the short life-time of the ultimate mutagen.
12 compounds which are constituents of hair dyes or chemically related aromatic amines, aminophenols, their nitroderivatives and aromatic hydroxyderivatives were examined for evidence of mutagenic potential by means of the micronucleus test. None of the compounds tested caused an increase in the incidence of micronucleated erythrocytes after oral dosing.
Explore the source record for details and available documents.
The effects of combinations of the chemical carcinogens, dimethylnitrosoamine (DMN) or N-methyl-N'-nitro-N'-nitrosoguanidine (MNNG), with the environmental pollutants, cadmium (Cd) or polychlorinated biphenyls (PCB) were examined by Schmidt's micronucleus method with ddY strain mice. DMN had a positive mutagenic effect by oral administration, with a dose response between 25 and 100 mg/kg body weight. MNNG gave a slight positive, though not consistent result, and seemed to be more sensitive at an earlier stage after administration of the drug. Cd was given for up to 7 days in drinking water as a solution of CdCl2 at concentrations of 3, 30 or 300 ppm as Cd. PCB was administered orally at 100 mg/kg daily for 6 days as a solution in corn oil, or subcutaneously injected in ethanol. Neither Cd nor PCB gave positive results in the micronucleus test. However, a synergistic positive effect of Cd with DMN was seen, but PCB with either of these nitrosamines was not positive.
Chinese hamsters were exposed to acetone, methyl ethyl ketone, ethyl acetate and 2-methoxy ethyl acetate, known to be strong inducers of aneuploidy in the yeast Saccharomyces cerevisiae. All solvents yielded negative results in the micronucleus test, whereas the vinca alkaloid vindesine--used as a positive control substance--proved to act as a spindle poison in mammals in vivo.
The mutagenic effect of carbimazol and methylthiouracil on mice fetal blood in the 15th and 16th day of intrauterine life, as compared to the effect on maternal bone marrow and control animals, was studied using the micronucleus test. The incidence of micronucleated cells was significantly higher in the fetal blood than in the maternal bone marrow. The finding demonstrates that the method of transplacentar mutagenesis is a reliable test for estimating the mutagenic risk of such drugs as carbimazol and methylthiouracil in current therapeutical use.
The bone-marrow micronucleus assay was used in mice to evaluate the mutagenic potential of cyanamide administered per os at doses of 10, 49 and 247 mg/kg. Bone-marrow smears were examined to find the incidence of micronucleated cells in 1000 polychromatic erythrocytes (PCE) and 1000 normochromatic erythrocytes ( NCE ). The ratio of NCE /PCE was also scored. No increase in the incidence of micronucleated polychromatic erythrocytes and no difference in the ratio NCE /PCE for the groups treated with cyanamide (10 and 49 mg/kg) were observed. The group treated with the highest dose of cyanamide (247 mg/kg) did, however, show an NCE /PCE ratio lower than the control group (p less than 0.05).
High doses of a test chemical sometimes affect the food consumption of the treated animals even to the point of starvation. The effect of such a non-specific toxicological stress on the bone marrow micronucleus test was investigated in male and female Sprague-Dawley rats. A 42-h starvation had a noticeable effect on the ratio of polychromatic to normochromatic erythrocytes (PCE and NCE); the values in the starved animals were approx. 77% of the negative controls. An effect of starvation on the frequency of micronucleated erythrocytes (MN-E) was not discernable from the results of the present experiment.
We have developed an in vivo micronucleus (MN) test that uses rat skin as the target organ. Sample preparation involves cold-treating the epidermis with trypsin, peeling it off with a fine forceps, treating it in hypotonic solution, and staining it with acridine orange (A.O.). We evaluated the assay using mitomycin C (MMC) and methyl methanesulfonate (MMS) as model clastogens, applying them as single and repeat treatments. Both chemicals induced a significant, dose-dependent increase in MN frequency in basal cells. One treatment per day for 3 days was optimal for MN induction.
Published data have suggested a possible link between the tumor promoting activity and the aneugenic properties of griseofulvin. The present study was conducted to explore this relationship. Griseofulvin was evaluated both for its potential promoting activity in liver carcinogenesis in partially hepatectomized F344 male rats initiated by diethylnitrosamine and for its genotoxic potential in the peripheral blood micronucleus assay. Rats were treated daily with 2,000 mg/kg body weight by oral gavage for 12 weeks in the medium-term carcinogenesis bioassay. GST-P-positive foci (mean number and surface area) and altered cell foci were compared in the liver of rats treated with griseofulvin alone, diethylnitrosamine alone,and griseofulvin in addition to diethylnitrosamine by using immunohistochemical and histopathological evaluation, respectively. This evaluation allowed the conclusion that griseofulvin did not initiate the carcinogenic process but rather had a potential in the liver for tumor promoting activity. Griseofulvin was found to be negative in the rat peripheral blood micronucleus test when given at a daily oral dose of 2,000 mg/kg body weight for at least 3 weeks.
Two preparations of maltitol (4-O-alpha-D-glucopyranosyl-D-sorbitol), hydrogenated glucose syrups and maltitol crystal, were examined for genotoxic potential by a battery of short-term tests. In the bacterial reversion assay, maltitol induced no detectable revertants in any of the tester strains, Salmonella typhimurium TA98, TA100, TA1535, TA1537, TA1538, or Escherichia coli WP2/pKM101 at doses of 0.5-50 mg per plate with and without rat liver S9 mix. In the micronucleus test, no significant increase in the frequency of micronucleated erythrocytes was observed in bone marrow of mice after administration of the two preparations at 3.75-30 g per kg by gastric intubation.
Administration of a single oral dose of instant coffee to Chinese hamsters at levels up to 2.5 g/kg body weight did not increase the frequency of sister chromatid exchanges. Furthermore, five consecutive daily oral doses of instant coffee given to Swiss OF-1 mice up to 3 g/kg/day did not induce increases in micronuclei above spontaneous levels. Similarly, no effect was observed in the micronucleus test after mice received two oral doses of coffee aroma of up to 50 ml/kg.
Because of its rapidness, simplicity and potential for automation, the measurement of micronucleated cells in vivo is not only equivalent to the analysis of chromosome aberrations, but often even preferred within routine genotoxicity testing. In order to evaluate the correlation between the in vitro micronucleus assay (MNT) and the in vitro chromosome aberration test (CA), we collected data from four pharmaceutical companies obtained either in Chinese hamster cell lines (CHO-K5, CHO-K1, V79) or in human peripheral blood lymphocytes. Among the 57 compounds included in this comparison, 45 compounds gave rise to concordant results in both assays (26 compounds negative in both assays; 19 compounds positive in both assays). The high percentage of concordance, i.e. about 79% is very promising and can be even increased to about 88% by omitting the 3 aneugenic compounds and 2 compounds inducing endoreduplicated chromosomes which were found positive only in the in vitro MNT. The results are remarkable in particular considering that most of the compounds evaluated are 'standard' pharmaceutical compounds and thus are at most weak inducers of chromosome damage. Our comparison strongly supports that the in vitro micronucleus test is a suitable alternative to the in vitro chromosome aberration assay. Moreover, the MNT has the potential of not only detecting clastogens but additionally aneuploidy inducing chemicals.
Sixteen carcinogens were evaluated in rats for their ability to induce micronuclei. The direct acting agent, ethyl methanesulfonate and the procarcinogens/promutagens, cyclophosphamide and 4-nitroquinoline-1-oxide, induced dose-related increases in micronucleated polychromatophilic erythrocytes. Aflatoxin B1 also significantly increased the number of micronucleated polychromatophillic erythrocytes for 2 doses although no dose-response could be detected. Dimethylnitrosamine produced variable results. The remaining 11 compounds, 2-acetylaminofluorene, 4-aminobiphenyl, benzidine, diethylnitrosamine, dimethylbenzanthracene, 1,2-dimethylhydrazine, ethionine, ethyl carbamate, hexametapol, metronidazole, and beta-naphthylamine, failed to induce significantly increased numbers of micronuclei. The large number of false negative results obtained in the present investigations using the micronucleus test suggests that in vivo cytogenetic assays utilizing bone marrow may also lack the sensitivity needed to detect clastogenic effects of procarcinogens/promutagens which require tissue specific metabolic activation.