Micronucleus

Nuclear medicine workers are occupationally exposed to chronic ionizing radiation. It is known that ionizing radiation may have damaging effects on chromosomes. In the present study, we investigated the genotoxic effects of ionizing radiation on nuclear medicine workers. We used two different indicators of genotoxicity methods: sister chromatid exchange (SCE) and micronucleus (MN).

The ethanolic extract of propolis, especially the Brazilian green type, is widely and mainly used for therapeutic purposes despite the lack of knowledge about its effects and its cellular mode of action. This type of propolis, derived from Baccharis dracunculifolia (alecrim-do-campo), has been extensively commercialized and the consumers use it to enhance health. This work aimed to assess the genotoxic/mutagenic and antigenotoxic/antimutagenic potential of the ethanolic extracts of Brazilian green propolis and of B. dracunculifolia, on mammalian cells. It was not observed genotoxic and mutagenic effect by both extracts. After evaluate the exposure of the cells to each extract with a recognized mutagen, simultaneously, the results showed a significant reduction on DNA damage. The experiment carried out with a pre-incubation period was more effective than without incubation test, showing that the tested extracts were able to inactivate the mutagen before it could react with the DNA.

Despite its antioxidant capacity and well-known health benefits, yerba mate tea (Ilex paraguariensis) has been shown to possess some genotoxic and mutagenic activities and to increase incidence of some types of cancer. The aim of this study was to estimate the cyto- and genotoxicity of mate tea in human peripheral lymphocytes in vitro. We found that yerba mate extract induced a concentration-dependent, statistically significant increase in the level of apoptotic and necrotic cells and a decrease in the nuclear division index (NDI). Mate-exposed lymphocytes had a reduced transcriptional rDNA activity, which may be due to the stress conditions, and showed an elevated production of micronuclei. The FISH technique revealed the appearance of an acrocentric signal in mate-induced micronuclei, which suggests that under these conditions yerba mate extract may display aneugenic activity. Since caffeine is one of the most abundant compounds found in the dry mass of mate, we conducted additional experiments with caffeine alone. We showed that caffeine used at the same concentrations manifests a more potent cyto- and genotoxic effect that may account, at least in part, for the disadvantageous effects observed for yerba mate extract.

El Sulfatiazol un miembro de la familia de las Sulfonas tiene potenciales efectos cancerígenos, en el presente estudio se evaluó por medio de la técnica de micronúcleos el daño al material genético en ratones tras ser expuestos a dicho compuesto, encontrandose un aumento en el numero de micronúcleos después de la aplicación del medicamento.

Nigella sativa has been traditionally used for the treatment of inflammations, liver disorders, and arthritis. Experimentally, it has been demonstrated that N. sativa extracts and the main constituent of their volatile oil, thymoquinone, possess antioxidant, anti-inflammatory and hepato-protective properties. To further evaluate the toxicological properties in a metabolically competent cellular system, thymo-quinone was applied to primary rat hepatocyte cultures, and both cyto-and genotoxic effects were tested. Mitotic indices and the rates of apoptoses and necroses were determined as endpoints of cytotox-icity, while chromosomal aberrations and micronucleated cells served as endpoints of genotoxicity. In this approach thymoquinone demonstrated cyto-and genotoxic effects in a concentration dependent manner: it induced significant anti-proliferative effects at 20 lM and acute cytotoxicity at higher concentrations. Thymoquinone significantly increased the rates of necrotic cells at concentrations between 2.5 and 20 lM. Furthermore, it induced significant genotoxicity at concentrations P1.25 lM. These observations support the previous finding that thymoquinone causes glutathione depletion and liver damage, but contradict the reports indicating antioxidant and anti-clastogenic effects. Thymoquinone might be metabolised to reactive species and increase oxidative stress, which contributes to the depletion of anti-oxidant enzymes and damage to DNA in hepatocytes treated with high thymoquinone concentrations.

Methylphenidate (MPH, Ritalin®), has been prescribed to treat attention deficit/hyperactivity disorder (ADHD) since its approval by the FDA over 50 years ago. Diagnoses of pediatric patients with ADHD and the administration of MPH to treat the symptoms have increased in prevalence in recent years. A 2005 study by El-Zein et al. reported statistically significant increases in cytogenetic anomalies including chromosomal aberrations (CA), micronuclei (MN) and sister chromatid exchanges (SCEs) in peripheral blood lymphocytes cultured from pediatric patients treated for 3 months with MPH. These findings led to wide-spread concern regarding the potential for genotoxic risks associated with prolonged administration of MPH. The study described in the present paper was designed to repeat the El-Zein effort with a much larger sample size. The subjects (N = 109) were randomized into two groups: one treated with MPH as well as behavior therapy, the other was a control group that received behavior therapy only. We evaluated CAs, MN, and SCEs in peripheral blood lymphocytes in samples obtained prior to therapy and after 3 months of treatment with MPH. The data were analyzed using a Poisson regression model with a generalized estimating equation method adjusted for several covariates including time, treatment-by-time interaction, sex, and age group. The loge rate ratios of the MPH plus behavior therapy and behavior therapy groups were compared. The frequencies of CAs, MN, and SCEs were not increased in the MPH plus behavior therapy group when compared to the behavior therapy group only (p = 0.53, 0.28, 0.81, respectively). These results provide evidence in a large cohort that MPH does not induce cytogenetic anomalies in children, in contrast to the findings of the El-Zein study.

The study of DNA damage at the chromosome level is an essential part of genetic toxicology because chromosomal mutation is an important event in carcinogenesis. The micronucleus assays have emerged as one of the preferred methods for assessing chromosome damage because they enable both chromosome loss and chromosome breakage to be measured reliably. Because micronuclei can only be expressed in cells that complete nuclear division a special method was developed that identifies such cells by their binucleate appearance when blocked from performing cytokinesis by cytochalasin-B (Cyt-B), a microfilament-assembly inhibitor. The cytokinesis-block micronucleus (CBMN) assay allows better precision because the data obtained are not confounded by altered cell division kinetics caused by cytotoxicity of agents tested or sub-optimal cell culture conditions. The method is now applied to various cell types for population monitoring of genetic damage, screening of chemicals for genotoxic potential...

Se evaluó la hipótesis planteada, donde la exposición mínima de 20 horas semanales a varios reactivos, soluciones y solventes durante las prácticas académicas, limpieza de almacén e inventario de reactivos, de docentes, trabajadores y alumnos de la FQIQ de la UNMSM ocasiona un incremento de biomarcadores de exposición y efecto temprano. La frecuencia de micronúcleos en la mucosa bucal fue analizada para comprobar el efecto citogenético y citotóxico en dos poblaciones: Grupo Problema y Grupo Control, en dos etapas. Por cada población se tomó tres grupos de un total de 85 individuos, Docentes (edad media: 56,6±6,48), trabajadores no docentes (edad media: 48,5±17,5) y estudiantes (edad media: 25,14±4,99). Se realizó el test de micronúcleo (Mn) en células epiteliales de la mucosa bucal, comparando los valores obtenidos de daño genotóxico y citotóxico para cada individuo y en cada toma de muestra; en el análisis estadístico se aplicó ANOVA con un valor de significancia de 95% de confiabilidad. Se encontró daño a nivel celular en la población problema en ambas etapas de la toma de muestra, principalmente a nivel de núcleo (aberraciones nucleares). El daño más frecuente en ambas etapas fue la anomalía de célula binucleada (26,70±16,44); seguido de células con cariólisis (7,17±5,89), picnosis (3,70±2,46) y “huevo roto” (3,17±3,92). No se  encontró relación con respecto a la edad de los grupos evaluados en ninguna de las dos tomas. En cuanto a la relación entre los tipos de estamentos universitarios, los trabajadores no docentes presentan mayor daño (47,00±16,46), seguido de los docentes (29,50±14,50) y los estudiantes (17,00±10,00). En conclusión, existe daño citotóxico, genotóxico y apoptótico en la población problema, probablemente por la exposición crónica de sustancias químicas que dañan la integridad del ADN celular.

Background, aim and scope The biocide triclosan (TCS) is commonly used in personal care, acrylic, plastic, and textiles products. TCS has been detected in surface water in several countries, and its ecological impact is largely unknown. In this work, the toxicity of TCS in zebrafish (Danio rerio), embryos and adults was studied. Several lethal and sub-lethal endpoints were analysed in organisms exposed to TCS such as mortality, embryo development and behaviour, hatching, micronuclei and biochemical markers (cholinesterase (ChE), glutathione S-transferase (GST) and lactate dehydrogenase (LDH)). Materials and methods Embryo/larvae assay followed the OECD guideline on Fish Embryo Toxicity Test. Embryos were exposed at nominal concentrations of 0.1, 0.3, 0.5, 0.7 and 0.9 mg/l of TCS for 6 days and were inspected daily with the help of a stereomicroscopy for mortality, developmental parameters (otolith formation, eye and body pigmentation, somite formation, heart beat, tail circulation, detachment of the tail-bud from the yolk sac) and hatching. A similar test was run to obtain larvae for ChE, GST and LDH analysis. The adult test followed the OECD Guideline TG 203 in semi-static conditions. Adult zebrafish of similar length and age were exposed to nominal concentrations of 0.1, 0.2, 0.3, 0.4 and 0.5 mg/l of TCS for 96 h and were inspected daily for mortality and behaviour alterations. A second test was run to obtain organs for biomarkers analysis: Heads, muscles and gills were isolated and snap-frozen in eppendorfs and used for ChE, LDH and GST determinations, respectively. Adult zebrafish testing also comprised a third test for micronucleus analysis in which the nominal concentrations of 0, 0.175 and 0.350 mg/l were used. Peripheral blood was obtained by cardiac puncture and used for the analysis. Results TCS showed acute toxicity for embryo/larvae (96 h LC50 = 0.42 mg/l) and delayed hatching. Moreover, embryo toxicity was evident: Delay on the otolith formation and eye and body pigmentation were found, and malformations were also evident, including spine malformations, pericardial oedema and undersize. Biomarkers levels were affected: ChE and LDH activity were increased in larvae exposed to 0.25 mg/l, and GST activity was increased in larvae exposed to 0.25 and 0.35 mg/l. TCS also demonstrated acute toxicity to adult zebrafish (96 h LC50 = 0.34 mg/l). However, TCS did not change biomarkers levels and did not elicit a micronucleus in adults. Discussions Despite the fact that similar 96 h LC50 values have been found for D. rerio embryos and adults (0.42 and 0.34 mg/l, respectively), the embryo assay was much more informative, showing important effects at several levels, including teratogenic response, hatching delay and alteration of biomarker levels. TCS does not seem to be genotoxic for adult fish or to interfere with biomarkers levels at the concentrations tested. Conclusions TCS has deleterious effects on zebrafish adults and during early stages, (including embryotoxicity, hatching delay and alterations of biomarkers levels). The range of endpoints used on the embryo test allows an integrated analysis that contributes to a better understanding of the toxicity and mode of action of TCS. Recommendations and perspectives Future works should focus on a deeper investigation of TCS modes of action on zebrafish early-life stages. As embryo testing was revealed to be so informative, a refinement of the test could be made, including other endpoints such as different biochemical markers as well as DNA microarrays to assess a gene expression level for the effect of exposure to TCS. In the perspective of risk assessment, these endpoints should be explored in order to assess their usefulness as early warning signs and links should be sought between these short-term tests and effects of long-term exposures as it is observed in more realistic scenarios.

Occupational exposures to hazardous chemicals are common in industries using solvent based materials as well as in indoor environments where people are exposed to volatile organic compounds from various sources. The health of the workers has several determinants, including risk factors at the workplace leading to cancer. The aim of the present investigation was to assess the potential cytogenetic damage associated with occupational exposure among pesticide workers by using micronuclei and other nuclear abnormalities as a biomarker. The micronucleus assay on exfoliated buccal cells is a useful and minimally invasive method for monitoring genetic damage in humans. To determine the genotoxic effects of pesticide workers, Micronucleus assay was carried out in exfoliated buccal cells of 50 pesticide workers and 50 controls. For each individual, 2,000 exfoliated buccal cells were analyzed. Micronucleus and other nuclear abnormalities frequencies in exposed were significantly higher than those in control groups (P<0.05) and also significantly related to smoking, tobacco chewing and alcohol drinking habit (P<0.05). Increased frequency of these nuclear abnormalities in buccal epithelial cells of exposed workers indicates adverse cellular reaction and/or a surveillance mechanism to eliminate cells with genetic damage. The present studied individuals may be at a higher risk of developing cancer and therefore monitored for any long term adverse effects of the exposure. Genotoxic studies are foremost for any occupational exposure studies. Evaluation based on genotoxic parameters is often useful in warranting environmental endowment and occupational health. Genotoxicity biomarkers have received a considerable interest as tools for detecting human genotoxic exposure and effects, especially in health surveillance programs dealing with chemical carcinogens.

Brazilian green propolis is a resinous substance prepared by bees from parts of the plant Baccharis dracunculifolia. As it possess several biological properties, this work assessed the cytotoxic/anticytotoxic, genotoxic/antigenotoxic and mutagenic/antimutagenic potential of ethanolic extracts of Brazilian green propolis (EEGP) and of B. dracunculifolia (EEBD), by means of the Allium cepa test system. The effects were evaluated by assessing the chro-mosomal aberrations (CA) and micronuclei (MN) frequencies on meristematic and F1 generation cells from onion roots. Chemical analyses performed with the extracts showed differences in flavonoid quality and quantity. No genotoxic or mutagenic potential was detected, and both extracts were capable of inhibiting cellular damage caused by methyl methanesulfonate (MMS) treatment, reducing the frequencies of CA and MN. By these data, we can infer that, independent of their flavonoid content, the extracts presented a protective effect in A. cepa cells against the clastogenicity of MMS.

Workers employed in petroleum refineries are exposed to a wide range of toxic compounds (benzene, polycyclic aromatic hydrocarbons, heavy metals, etc.) with known mutagenic and carcinogenic potential. In this study, we investigated by using the cytokinesis block micronucleus (CBMN) assay on human peripheral blood lymphocytes (PBL) whether general occupational exposure in petroleum refineries resulted in early biological effects, which would be indicative of adverse health effects in the long term. In this study, out of more 500 workers enrolled in the study, 79 male subjects (46 nonsmokers and 33 smokers), employed in two different Italian petroleum refineries, and a total of 50 male control subjects (34 nonsmokers and 16 smokers) were selected by using very strict selection criteria. The comparison of chromosome damage in PBL between exposed and control populations pointed out a significant increase of micronuclei in the exposed group, correlated with the length of employment. Resu...

Environmental impact assessment studies highlight the harmful effect of toxicants such as pesticides, heavy metals and industrial wastes on target and non-target species including birds. The effect of toxicant exposure on birds was used as an assessment of environmental contamination. The presence of micronucleus was investigated as a biomarker of genotoxicity in free-ranged village weavers captured within Ibadan Metropolis, Nigeria. Micronucleus assay was done using bone marrow collected from tibia and femur post-mortem. The clinical, haematologic, and biochemical changes were also monitored. The haemocytometric method was used to evaluate the erythrogram and leucogram changes. Microscopy was used for histopathology. It was discovered that 20% of the village weavers were positive for micronucleus while 80% were negative for micronucleus. The tissue changes observed in this study also underscore toxicity to possible environmental toxicants. In this study, micronucleus assay was used to evaluate the possibility of exposure of village weavers to genotoxic substances.

Context: Sacha Inchi has been consumed for years by indigenous peoples. Meanwhile, its toxicological potential has not been sufficiently studied.

Aims: To assess the acute, sub-chronic toxicity and genotoxicity evaluation of Sacha Inchi powder obtained from Plukenetia volubilis L.

Methods: A dose of 2000 mg/kg was orally administered to rats and mice and toxicity symptoms for 14 days were observed. In repeated dose study, the product was orally administered to Sprague Dawley rats of both sexes. Animals received 50, 250 and 500 mg/kg/day of the product for 90 days. At the end, animals were sacrificed and samples were done for hematological and biochemical analysis, organ weighs and histopathological examination. Genotoxicity potential of Sacha Inchi powder was evaluated through micronucleus test in mice. Negative controls received the vehicle (carboxymethyl cellulose, 0.5%) used.

Results: No morbidity or mortality at 2000 mg/kg of the product were found. Sacha Inchi powder oral administration during 90 days to rats did not lead to death, body weight gain, food consumption, or adverse events. No significant changes on hematological or biochemical parameters, organ weights or histopathological findings were observed. Induction of micronucleus formation attributable to the product was not found in mice.

Conclusions: No toxicity effects after oral acute exposure of Sacha Inchi power to rats and mice were observed. Neither toxicity attributable to oral doses of the product up to 500 mg/kg during 90 days to rats were found. Results suggested Sacha Inchi powder does not have genotoxicity potential under our experimental conditions.