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PubMed2003

Cytogenetic biomonitoring in petrol station attendants: micronucleus test in exfoliated buccal cells.

To study the effects of occupational exposure to petroleum derivates such as benzene, exfoliated buccal cells from 50 petrol station attendants and 50 age- and sex-matched control subjects were examined for micronucleus (MN) frequency. Frequencies of nuclear abnormalities (NA) other than micronuclei, such as binucleates, karyorrhexis and karyolysis, were also evaluated. Benzene exposure was ascertained by measuring urinary phenol levels. The mean urinary phenol level of station workers was found to be significantly higher than that of control subjects (P < 0.05). Analysis of buccal cells revealed that MN and NA frequencies in petrol station workers were significantly higher than in control subjects (P < 0.01) and also significantly related to smoking habit (P < 0.01). Our findings indicate that the petrol station workers are under risk of significant cytogenetic damage.

Adult↗
PubMed1990

The in vivo erythrocyte micronucleus test: measurement at steady state increases assay efficiency and permits integration with toxicity studies.

The mouse erythrocyte micronucleus assay has been traditionally carried out using one or two exposures to the test agent, followed by sampling at two or three postexposure times to obtain a sample near the time of the transient peak of micronucleated polychromatic erythrocytes (PCEs). We have demonstrated that frequencies of micronucleated RNA-positive (PCEs) and RNA-negative erythrocytes in blood and bone marrow come to steady state during "continuous" exposure via diet or drinking water, or during repeated daily exposures to test agents by ip injection, gavage, or inhalation. Under these exposure conditions, frequencies of micronucleated cells in peripheral blood approached steady state within 2-3 days in RNA-positive erythrocytes and in 5-6 weeks in RNA-negative erythrocytes. With exposure durations of 6 days (monocrotaline or Crotalaria seeds in diet), 10 days (triethylenemelamine, mitomycin C, 7,12-dimethylbenzanthracene, or colchicine, ip daily), 90 days (triethylenemelamine or urethan in drinking water or 1,3-butadiene via inhalation), or 2 years (benezene by daily gavage), frequencies of micronucleated cells attained and remained at steady state for prolonged periods. At steady state, frequencies of micronucleated RNA-positive cells in bone marrow samples were similar to those in RNA-positive and RNA-negative cells in peripheral blood (e.g., triethylenemelamine in drinking water at 4 micrograms/ml resulted in frequencies of micronucleated RNA-negative erythrocytes in peripheral blood of 27/1000 after 45 days of exposure and 24/1000 after 90 days, with a frequency of 28/1000 in bone marrow RNA-positive erythrocytes after 90 days). The data suggest that the efficiency of the assay would be markedly improved by using a repeated dose schedule with a single sample taken at steady state, rather than scoring multiple samples at various times after a single dose. This approach allows the frequency of micronucleated cells to be measured in a sample of bone marrow or blood obtained at almost any stage of routine toxicity testing.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2003

Mouse bone marrow micronucleus test results do not predict the germ cell mutagenicity of N-hydroxymethylacrylamide in the mouse dominant lethal assay.

N-Hydroxymethylacrylamide (NHMA), a mouse carcinogen inactive in the Salmonella assay and mouse micronucleus (MN) assay, was tested for reproductive effects in a mouse continuous breeding study. In that study, increased embryonic deaths were observed after 13 weeks exposure of parental animals to NHMA via drinking water (highest dose, 360 ppm); the results indicated the possible induction of chromosome damage in germ cells of treated males. An additional mouse MN test was conducted using a 31-day treatment period to better match the dosing regimen used in the breeding study; the results were negative. Additional studies were conducted to explore the germ cell activity of NHMA. A male mouse dominant lethal study was conducted using a single intraperitoneal injection of 150 mg/kg NHMA; the results were negative. A follow-up study was conducted using fractionated dosing, 50 mg/kg/day for 5 days; again, no increase in dominant lethal mutations was observed. NHMA (180-720 ppm) was then administered to male mice in drinking water for 13 weeks, during which three sets of matings occurred. Two weeks after mating, females were killed and the uterine contents were analyzed. Large, dose-related increases in dominant lethal mutations were observed with increasing length of exposure. The magnitude of the increases stabilized after 8 weeks of treatment. However, the frequency of micronucleated peripheral blood erythrocytes was not elevated in mice treated for 13 weeks with NHMA in drinking water. Thus, NHMA appears to be unique in inducing genetic damage in germ cells but not somatic cells of male mice.

Acrylamides↗
PubMed2004

Lack of genotoxicity of potassium iodate in the alkaline comet assay and in the cytokinesis-block micronucleus test. Comparison to potassium bromate.

Iodine could be added to the diet of human population in the form of iodide or iodate but iodate had not been adequately tested for genotoxicity and carcinogenicity. In the present study, genotoxic effects of potassium iodate were evaluated in vitro using the alkaline comet assay and the cytokinesis-block micronucleus assay on CHO cells and compared to halogenate salt analogues potassium bromate and chlorate and also to their respective reduced forms (potassium iodide, bromide and chloride). The results showed that the comet assay failed to detect the presence of DNA damage after a treatment of cells by potassium iodate for concentrations up to 10 mM. This absence of primary DNA damage was confirmed in the cytokinesis-block micronucleus assay. In the same way, results showed that potassium chlorate as well as potassium iodide, bromide and chloride did not induced DNA damage in the alkaline comet assay for doses up to 10 mM. By contrast, potassium bromate exposure led to an increase in both DNA damage and frequency of micronucleated cells. The repair of bromate-induced DNA damage was incomplete 24 h after the end of treatment. These results seem to indicate that potassium bromate would induce DNA damage by several mechanisms besides oxidative stress.

Animals↗
PubMed1990

[The micronucleus test in human peripheral lymphocytes].

A new methodology is reported determining the cytogenetic damage in stimulated human peripheral lymphocytes. The methodology is based on the investigation of the frequency of cells with micronuclei utilizing cytochalasin B. The spontaneous frequency of cells with micronuclei in the group of healthy volunteers (9 females and 3 males) of the mean age of 37.8 years was 18.42 micronuclei/1000 cells. Furthermore, the action of the analgesic agent paracetamol on the frequency of cells with micronuclei was examined; after the dose of 3 X 1000 mg of paracetamol administered within 8 h no increase in the occurrence of micronuclei within 1 week was found. The advantage of the use of the test for the determination of micronuclei with cytochalasin B in the testing of new drugs are discussed.

Acetaminophen↗
PubMed1998

[Importance of micronucleus tests in cultured binuclear T lymphocytes for the detection of genotoxic events in cancer patients].

The cytokinesis-blocked micronucleus assay (CBMN) is a short-term mutagenesis test which offers an easier and less tedious alternative to metaphase chromosome analysis, with the advantage that exposure to both clastogens and aneugens may be detected. The CBMN assay has been used in evaluating the genotoxic consequences of exposures to environmental and occupational mutagens and carcinogens. Micronucleated cell rates (MN cell rates) were assessed in cytokinesis-blocked lymphocytes of 70 male and female cancer patients prior to any anticancer treatment. The study of interindividual variation factors showed that only age significantly affect MN cell rate, whereas sex, tobacco, alcohol, imaging techniques and tumour stage had no significant effect. The comparison of micronucleated cell rates in 198 healthy subjects and 70 cancer patients matched for age and sex showed a statistically significant difference. Spontaneous elevated MN cell rates of cancer patients refer to previous exposition of genotoxic or mutagenic environmental agents. Moreover, the MN cell rates in cancer patients most probably refers to various cellular lesions and genetic damages.

Adult↗
PubMed2006

Micronucleus test and observation of nuclear alterations in erythrocytes of Nile tilapia exposed to waters affected by refinery effluent.

Micronuclei and nuclear alterations tests were performed on erythrocytes of Oreochromis niloticus (Perciformes, Cichlidae) in order to evaluate the water quality from Paraíba do Sul river, in an area affected by effluents from an oil shale processing plant, located in the city of São José dos Campos, Brazil-SP. Water samples were collected on 2004 May and August (dry season) and on 2004 November and 2005 January (rain season), in three distinct sites, comprising 12 samples. It was possible to detect substances of clastogenic and/or aneugenic potential, as well as cytotoxic substances, chiefly at the point corresponding to the drainage of oil shale plant wastes along the river. The highest incidence of micronuclei and nuclear alterations was detected during May and August, whereas the results obtained in November and January were insignificant. This work shows that the effluent treatment provided by the oil shale plant was not fully efficient to minimize the effect of cytotoxic and mutagenic substances in the test organism surveyed.

Aneugens↗