Genetic damage in coal and uranium miners.

Mining has a direct impact on the environment and on the health of miners and is considered one of the most hazardous occupations worldwide. Miners are exposed to several occupational health risks, including genotoxic substances, which may cause adverse health effects, such as cancer. This review summarizes the relation between DNA damage and mining activities, focusing on coal and uranium miners. The search was performed using electronic databases, including original surveys reporting genetic damage in miners. Additionally, a temporal bibliometric analysis was performed using an electronic database to create a map of cooccurrence terms. The majority of studies were performed with regard to occupational exposure to coal, whereas genetic damage was assessed mainly through chromosomal aberrations (CAs), micronuclei (MNs) and comet assays. The bibliometric analysis demonstrated associations of coal exposure with silicosis and pneumoconiosis, uranium miners with lung cancer and tumors and some associated factors, such as age, smoking, working time and exposure to radiation. Significantly higher DNA damage in miners compared to nonexposed groups was observed in most of the studies. The timeline reveals that classic biomarkers (comet assay, micronucleus test and chromosomal aberrations) are still important tools to assess genotoxic/mutagenic damage in occupationally exposed miners; however, newer studies concerning genetic polymorphisms and epigenetic changes in miners are being conducted. A major challenge is to investigate further associations between miners and DNA damage and to encourage further studies with miners of other types of ores.

Reduced fertility caused by meiotic defects and micronuclei formation during microsporogenesis in xBrassicoraphanus.

BACKGROUND: Hybridization and polyploidization events are important driving forces in plant evolution. Allopolyploids formed between different species can be naturally or artificially created but often suffer from genetic instability and infertility in successive generations. xBrassicoraphanus is an intergeneric allopolyploid obtained from a cross between Brassica rapa and Raphanus sativus, providing a useful resource for genetic and genomic study in hybrid species. OBJECTIVE: The current study aims to understand the cause of hybrid sterility and pollen abnormality in different lines of synthetic xBrassicoraphanus from the cytogenetic perspective. METHODS: Alexander staining was used to assess the pollen viability. Cytogenetic analysis was employed to monitor meiotic chromosome behaviors in pollen mother cells (PMCs). Origins of parental chromosomes in xBrassicoraphanus meiocytes were determined by genome in situ hybridization analysis. RESULTS: The xBrassicoraphanus lines BB#4 and BB#6 showed high rates of seed abortion and pollen deformation. Abnormal chromosome behaviors were observed in their PMCs, frequently forming univalents and inter-chromosomal bridges during meiosis. A positive correlation also exists between meiotic defects and the formation of micronuclei, which is conceivably responsible for unbalanced gamete production and pollen sterility. CONCLUSION: These results suggest that unequal segregation of meiotic chromosomes, due in part to non-homologous interactions, is responsible for micronuclei and unbalanced gamete formation, eventually leading to pollen degeneration and inferior fertility in unstable xBrassicoraphanus lines.

Manool, a diterpene from Salvia officinalis, exerts preventive effects on chromosomal damage and preneoplastic lesions.

The present study aimed to evaluate the effect of the manool diterpene on genomic integrity. For this purpose, we evaluated the influence of manool on genotoxicity induced by mutagens with different mechanisms of action, as well as on colon carcinogenesis. The results showed that manool (0.5 and 1.0 µg/ml) significantly reduced the frequency of micronuclei induced by doxorubicin (DXR) and hydrogen peroxide in V79 cells but did not influence genotoxicity induced by etoposide. Mice receiving manool (1.25 mg/kg) exhibited a significant reduction (79.5%) in DXR-induced chromosomal damage. The higher doses of manool (5.0 and 20 mg/kg) did not influence the genotoxicity induced by DXR. The anticarcinogenic effect of manool (0.3125, 1.25 and 5.0 mg/kg) was also observed against preneoplastic lesions chemically induced in rat colon. A gradual increase in manool doses did not cause a proportional reduction of preneoplastic lesions, thus demonstrating the absence of a dose-response relationship. The analysis of serum biochemical indicators revealed the absence of hepatotoxicity and nephrotoxicity of treatments. To explore the chemopreventive mechanisms of manool via anti-inflammatory pathways, we evaluated its effect on nitric oxide (NO) production and on the expression of the NF-kB gene. At the highest concentration tested (4 µg/ml), manool significantly increased NO production when compared to the negative control. On the other hand, in the prophylactic treatment model, manool (0.5 and 1.0 µg/ml) was able to significantly reduce NO levels produced by macrophages stimulated with lipopolysaccharide. Analysis of NF-kB in hepatic and renal tissues of mice treated with manool and DXR revealed that the mutagen was unable to stimulate expression of the gene. In conclusion, manool possesses antigenotoxic and anticarcinogenic effects and its anti-inflammatory potential might be related, at least in part, to its chemopreventive activity.

Multiple-endpoint in vitro carcinogenicity test in human cell line TK6 distinguishes carcinogens from non-carcinogens and highlights mechanisms of action.

Current in vitro genotoxicity tests can produce misleading positive results, indicating an inability to effectively predict a compound's subsequent carcinogenic potential in vivo. Such oversensitivity can incur unnecessary in vivo tests to further investigate positive in vitro results, supporting the need to improve in vitro tests to better inform risk assessment. It is increasingly acknowledged that more informative in vitro tests using multiple endpoints may support the correct identification of carcinogenic potential. The present study, therefore, employed a holistic, multiple-endpoint approach using low doses of selected carcinogens and non-carcinogens (0.001-770 µM) to assess whether these chemicals caused perturbations in molecular and cellular endpoints relating to the Hallmarks of Cancer. Endpoints included micronucleus induction, alterations in gene expression, cell cycle dynamics, cell morphology and bioenergetics in the human lymphoblastoid cell line TK6. Carcinogens ochratoxin A and oestradiol produced greater Integrated Signature of Carcinogenicity scores for the combined endpoints than the "misleading" in vitro positive compounds, quercetin, 2,4-dichlorophenol and quinacrine dihydrochloride and toxic non-carcinogens, caffeine, cycloheximide and phenformin HCl. This study provides compelling evidence that carcinogens can successfully be distinguished from non-carcinogens using a holistic in vitro test system. Avoidance of misleading in vitro outcomes could lead to the reduction and replacement of animals in carcinogenicity testing.

Protective effects of Bidens pilosa on hepatoxicity and nephrotoxicity induced by carbon tetrachloride in rats.

The aim of this study was to assess the protective effects of oral and topical treatment with Bidens pilosa (BP) against carbon tetrachloride (CCl4)- induced toxicity. Fifty-six rats were divided into seven groups: A: CCl4 only; B: CCl4+oral BP; C: CCl4 and topical BP; D: CCl4+oral and topical BP; E: oral BP only; F: negative control; and G: positive control (cyclophosphamide). The animals were treated for 10 weeks. Blood samples were collected for tests of hepatic and renal function, and fragments of the liver, spleen, pancreas, kidney, and intestine were collected for histopathological analyses. Cells from the femoral bone marrow were used for a micronucleus test and 'comet assay'. Statistically significant differences were observed in the levels of gamma-glutamyl transpeptidase (GGT), albumin, urea and creatinine, hepatic inflammation, renal tubular lesion, and inflammation of the intestinal mucosa between the BP-treated groups and untreated group. The median number of micronuclei in group A was 4.00, in group G was 9.00 and in the other groups was 0.00. Group A had the lowest number of cells with a score of 0 and the greatest number with scores of 3 and 4, similar to the results obtained from group G using the 'comet assay'. Thus, BP effectively protected against the toxic effects of CCl4 on the liver, kidney, and intestine and exerted an antimutagenic effect on rats exposed to CCl4.

Low-polar extract from seed of Cleistocalyx nervosum var. paniala modulates initiation and promotion stages of chemically-induced carcinogenesis in rats.

BACKGROUND: Cleistocalyx nervosum var. paniala is a local fruit mainly cultivated in the north of Thailand. Our previous study has reported that the methanol extract of C. nervosum seed presented antimutagenicity in a Salmonella mutation assay. The present study focused on the effect of a low-polar extract of C. nervosum seed on the early stages of diethylnitrosamine (DEN)- and dimethylhydrazine (DMH)-induced carcinogenesis in rats. METHODS: Dried C. nervosum seed powder was extracted using dichloromethane. To study its effect on the initiation stage of carcinogenesis of rats, they were fed with various doses of C. nervosum seed extract (CSE) for 21 days. DEN injection was used to initiate hepatocarcinogenesis and partial hepatectomy was performed to amplify mutated hepatocytes resulting in micronucleated hepatocyte formation. To study the role of CSE on the promotion stage, rats were injected with DEN and DMH to induce preneoplastic lesions and the numbers of glutathione S-transferase placental form (GST-P) positive foci in the liver and aberrant crypt foci (ACF) in the colon were measured. This was followed by CSE administration for 10 weeks. The inhibitory mechanisms of CSE on initiation and promotion stages, including xenobiotic metabolism, cell proliferation and apoptosis, were investigated. RESULTS: The total phenolic content in CSE was 80.34 ± 2.29 mg gallic acid equivalents (GAE) per g of extract and 2,4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone was found to be a major flavonoid. The main terpenoids in CSE were ß-selinene, α-selinene, γ-selinene and o-cymene while 24(Z)-methyl-25-homocholesterol was a major phytosterol. CSE significantly decreased the number of micronucleated hepatocytes in DEN-initiated rats and enhanced the activities of hepatic glutathione S-transferase and UDP-glucuronyltransferase. Furthermore, the formation of preneoplastic lesions in the liver and colon was statistically reduced by CSE. CSE also diminished cell proliferation in the liver and colon indicated by the number of PCNA positive cells. However, CSE did not alter the numbers of apoptotic hepatocytes and colonocytes in DEN- and DMH-initiated rats. CONCLUSIONS: The dichloromethane extract of C. nervosum seed demonstrated chemopreventive effects on chemically-induced carcinogenesis in both initiation and promotion stages in rats. The inhibitory mechanism might be involved in the modulation of hepatic detoxifying enzymes and suppression of hepatocyte and colonocyte proliferation.

Genotoxicity studies with an ethanolic extract of Kalanchoe pinnata leaves.

Kalanchoe pinnata is a medicinal plant, used mainly in African, Brazilian, and Indian traditional medicine for the treatment of several human disorders. Whole leaf extracts, crude juice of the leaves, and aqueous and organic extracts of the leaves are used. Over the last decade, ethanolic extracts have become the most popular form of Kalanchoe medicinal preparation. In this study, an ethanolic extract of this plant leaf was tested in a battery of standard regulatory genetic toxicology tests. This extract did not induce reverse mutations in the Salmonella/microsome assay but induces a weak genotoxic response in the mouse lymphoma assay and the in vivo micronucleus assay in mice. Our results indicate that this material may cause DNA damage, and its use should be restricted.

Structure-dependent genotoxic potencies of selected pyrrolizidine alkaloids in metabolically competent HepG2 cells.

1,2-unsaturated pyrrolizidine alkaloids (PAs) are natural plant constituents comprising more than 600 different structures. A major source of human exposure is thought to be cross-contamination of food, feed and phytomedicines with PA plants. In humans, laboratory and farm animals, certain PAs exert pronounced liver toxicity and can induce malignant liver tumors in rodents. Here, we investigated the cytotoxicity and genotoxicity of eleven PAs belonging to different structural classes. Although all PAs were negative in the fluctuation Ames test in Salmonella, they were cytotoxic and induced micronuclei in human HepG2 hepatoblastoma cells over-expressing human cytochrome P450 3A4. Lasiocarpine and cyclic diesters except monocrotaline were the most potent congeners both in cytotoxicity and micronucleus assays with concentrations below 3 µM inducing a doubling in micronuclei counts. Other open di-esters and all monoesters exhibited weaker or much weaker geno- and cytotoxicity. The findings were in agreement with recently suggested interim Relative Potency (iREP) factors with the exceptions of europine and monocrotaline. A more detailed micronuclei analysis at low concentrations of lasiocarpine, retrorsine or senecionine indicated that pronounced hypolinearity of the concentration-response curves was evident for retrorsine and senecionine but not for lasiocarpine. Our findings show that the genotoxic and cytotoxic potencies of PAs in a human hepatic cell line vary in a structure-dependent manner. Both the low potency of monoesters and the shape of prototype concentration-response relationships warrant a substance- and structure-specific approach in the risk assessment of PAs.

Melatonin supplementation over different time periods until ageing modulates genotoxic parameters in mice.

The ageing process is a multifactorial phenomenon, associated with decreased physiological and cellular functions and an increased propensity for various degenerative diseases. Studies on melatonin (N-acetyl-5-methoxytryptamine), a potent antioxidant, are gaining attention since melatonin production declines with advancing age. Hence, the aim of this study was to evaluate the effects of chronic melatonin consumption on genotoxic and mutagenic parameters of old Swiss mice. Herein, 3-month-old Swiss albino male mice (n = 240) were divided into eight groups and subdivided into two experiments: first (three groups): natural ageing experiment; second (five groups): animals that started water or melatonin supplementation at different ages (3, 6, 12 and 18 months) until 21 months. After 21 months, the animals from the second experiment were euthanized to perform the comet assay, micronucleus test and western blot analysis. The results demonstrated that melatonin prolonged the life span of the animals. Relative to genomic instability, melatonin was effective in reducing DNA damage caused by ageing, presenting antigenotoxic and antimutagenic activities, independently of initiation age. The group receiving melatonin for 18 months had high levels of APE1 and OGG1 repair enzymes. Conclusively, melatonin presents an efficient antioxidant mechanism aiding modulating genetic and physiological alterations due to ageing.

Genotoxicity and Oxidative Stress Evaluations in Juvenile African Catfish Clarias gariepinus Exposed to NPK Fertilizer.

Juvenile African Catfish (also known as Sharptooth Catfish) Clarias gariepinus were exposed to 2.26, 4.52, and 11.30 mg/L NPK (15-15-15) fertilizer for 21 d followed by 7 d of recovery to assess the genotoxic effects of the fertilizer in erythrocytes. Biomarkers of oxidative stress were evaluated in the liver and gill tissues. The fertilizer induced micronuclei formation with maximum effects on day 7 in erythrocytes of individuals that were exposed to 4.52 and 11.30 mg/L NPK, and on day 14 in individuals exposed to 2.26 mg/L of the same fertilizer. The lipid peroxidation, glutathione reductase, and reduced glutathione values in the exposed fish increased, while the values of catalase, superoxide dismutase, and glutathione peroxidase decreased. There were mixed trends in the recovery patterns after the 7-d withdrawal from the fertilizer. Careful use of the fertilizer in the field is recommended to avoid toxicological effects on nontarget organisms.

Toxicogenetic evaluation of Smallanthus sonchifolius (yacon) as a herbal medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: Smallanthus sonchifolius (Poepp. & Endl.) H. Robinson, commonly known as yacon, is a medicinal plant belonging to the Asteraceae family used in traditional folk medicine. Its roots and leaves have been used by people suffering from diabetes or from various digestive or renal disorders. AIM OF THE STUDY: This study aimed at evaluating the in vitro potential genotoxic effects of the aqueous extract of yacon in order to determine its safety and at characterizing its phytochemical composition. MATERIALS AND METHODS: The aqueous extract of S. sonchifolius was prepared in a similar way to that commonly used in popular medicine as tea bags. Thin layer chromatography (TLC) and high-performance liquid chromatography (HPLC-MS/MS) were used to identify the main compounds. The MTT test was performed to determine the range of doses and the Cytochalasine B-blocked micronucleus (Cytome assay) was used to assess geneotoxicity. RESULTS: The chemical analysis of the aqueous extract revealed the presence of the sesquiterpene lactones (STLs) enhydrin and the dimer enhydrofolin, as the main compounds together with phenolic compounds. Increasing concentrations of the extract induced a cytotoxic effect on CHO-K1 and HepG2 cells. A statistically significant increase in the frequency of MNi, NBUDs and NPBs was observed in CHO-K1 cells, while in HepG2 cells a statistically significant frequency increase was observed with three of the four tested doses for MNi and only with the highest dose for NPBs and NBUs (genotoxic effect). CONCLUSION: Results demonstrated the inability of the metabolic system to counteract the genetic instability, allowing the safe consumption of the leaves as a 2% tea infusion in quantities of up to 250 mL/day.

Genotoxicity of the food additive E171, titanium dioxide, in the plants Lens culinaris L. and Allium cepa L.

E171 (titanium dioxide, TiO2), an authorized foods and beverage additive, is also used in food packaging and in pharmaceutical and cosmetic preparations. E171 is considered to be an inert and non-digestible material, not storable in animal tissues, but the possible presence of TiO2 nanoparticles (NP) may present a risk to human health and the environment. We determined the presence of 15% TiO2 NP in a commercial E171 food additive product, by electron microscopy. The biological effects of E171 were assessed in Lens culinaris and Allium cepa for the following endpoints: percentage of germination, root elongation, mitotic index, presence of chromosomal abnormalities, and micronuclei. The results indicated low phytotoxicity but dose-dependent genotoxicity. We also observed internalization of TiO2 NP and ultrastructural alterations in the root systems.

Cadmium and nickel co-exposure exacerbates genotoxicity and not oxido-inflammatory stress in liver and kidney of rats: Protective role of omega-3 fatty acid.

The present study examined the influence of co-exposure to cadmium (Cd) and nickel (Ni) on hepatorenal function as well as the protective role of omega-3 polyunsaturated fatty acids (ω-3FA) in rats. The animals were exposed to Cd (5 mg/kg) and Ni (150 µg/L in drinking water) singly or co-exposed to both metals and ω-3FA at 20 mg/kg for 14 consecutive days. Results showed that hepatorenal injury resulting from individual exposure to Cd or Ni was not aggravated in the co-exposure group. Moreover, ω-3FA markedly abrogated the reduction in the antioxidant enzyme activities, the increase in reactive oxygen and nitrogen species, and lipid peroxidation induced by Cd and Ni co-exposure. Additionally, ω-3FA administration markedly suppressed the increase in hepatic and renal myeloperoxidase activity, nitric oxide, tumor necrosis factor alpha, and interleukin-1 ß levels in the co-exposure group. Genotoxicity resulting from individual exposure to Cd or Ni was intensified in the co-exposure group. However, ω-3FA administration markedly ameliorated the genotoxicity and histological lesions in the co-exposure group. Taken together, co-exposure to Cd and Ni aggravated genotoxicity and not oxido-inflammatory stress in the liver and kidney of rats. ω-3FA abated hepatorenal injury and genotoxicity induced by Cd and Ni co-exposure in rats.

Inhibitory effect of purple rice husk extract on AFB1-induced micronucleus formation in rat liver through modulation of xenobiotic metabolizing enzymes.

BACKGROUND: Rice husk, a waste material produced during milling, contains numerous phytochemicals that may be sources of cancer chemopreventive agents. Various biological activities of white and colored rice husk have been reported. However, there are few comparative studies of the cancer chemopreventive effects of white and colored rice husk. METHODS: This study investigated the cancer chemopreventive activities of two different colors of rice husk using in vitro and in vivo models. A bacterial mutation assay using Salmonella typhimurium strains TA98 and TA100 was performed; enzyme induction activity in murine hepatoma cells was measured, and a liver micronucleus test was performed in male Wistar rats. RESULTS: The white rice husk (WRHE) and purple rice husk (PRHE) extracts were not mutagenic in Salmonella typhimurium TA98 or TA100 in the presence or absence of metabolic activation. However, the extracts exhibited antimutagenicity against aflatoxin B1 (AFB1) and 2-amino-3,4 dimethylimidazo[4,5-f]quinolone (MeIQ) in a Salmonella mutation assay. The extracts also induced anticarcinogenic enzyme activity in a murine Hepa1c1c7 hepatoma cell line. Interestingly, PRHE but not WRHE exhibited antigenotoxicity in the rat liver micronucleus test. PRHE significantly decreased the number of micronucleated hepatocytes in AFB1-initiated rats. PRHE contained higher amounts of phenolic compounds and vitamin E than WRHE in both tocopherols and tocotrienols as well as polyphenol such as cyanidin-3-glucoside, protocatechuic acid and vanillic acid. Furthermore, PRHE increased CYP1A1 and 1A2 activities while decreasing CYP3A2 activity in the livers of AFB1-treated rats. PRHE also enhanced various detoxifying enzyme activities, including glutathione S-transferase, NAD(P)H quinone oxidoreductase and heme oxygenase. CONCLUSIONS: PRHE showed potent cancer chemopreventive activity in a rat liver micronucleus assay through modulation of phase I and II xenobiotic metabolizing enzymes involved in AFB1 metabolism. Vitamin E and phenolic compounds may be candidate antimutagens in purple rice husk.

Co-carcinogenic effects of vitamin E in prostate.

A large number of basic researches and observational studies suggested the cancer preventive activity of vitamin E, but large-scale human intervention trials have yielded disappointing results and actually showed a higher incidence of prostate cancer although the mechanisms underlying the increased risk remain largely unknown. Here we show through in vitro and in vivo studies that vitamin E produces a marked inductive effect on carcinogen-bioactivating enzymes and a pro-oxidant status promoting both DNA damage and cell transformation frequency. First, we found that vitamin E in the human prostate epithelial RWPE-1 cell line has the remarkable ability to upregulate the expression of various phase-I activating cytochrome P450 (CYP) enzymes, including activators of polycyclic aromatic hydrocarbons (PAHs), giving rise to supraphysiological levels of reactive oxygen species. Furthermore, our rat model confirmed that vitamin E in the prostate has a powerful booster effect on CYP enzymes associated with the generation of oxidative stress, thereby favoring lipid-derived electrophile spread that covalently modifies proteins. We show that vitamin E not only causes DNA damage but also promotes cell transformation frequency induced by the PAH-prototype benzo[a]pyrene. Our findings might explain why dietary supplementation with vitamin E increases the prostate cancer risk among healthy men.

Aloe vera modulates X-ray induced hematological and splenic tissue damage in mice.

The present study was premeditated to examine the radioprotective effects of aqueous Aloe vera gel extract against whole-body X-ray irradiation-induced hematological alterations and splenic tissue injury in mice. Healthy male balb/c mice were divided into four groups: group 1, control; group 2, A. vera (50 mg/kg body weight) administered per oral on alternate days for 30 days (15 times); group 3, X-ray exposure of 2 Gy (0.25 Gy twice a day for four consecutive days in the last week of the experimental protocol); and group 4, A. vera + X-ray. X-ray exposure caused alterations in histoarchitecture of spleen along with enhanced clastogenic damage as assessed by micronucleus formation and apoptotic index. Irradiation caused an elevation in proinflammatory cytokines like tumor necrosis factor and interleukin-6, total leucocyte counts, neutrophil counts and decreased platelet counts along with unaltered red blood cell counts and hemoglobin. Irradiation also caused an elevation in reactive oxygen species (ROS), lipid peroxidation (LPO) levels, lactate dehydrogenase activity and alterations in enzymatic and nonenzymatic antioxidant defense mechanism in plasma and spleen. However, administration of A. vera gel extract ameliorated X-ray irradiation-induced elevation in ROS/LPO levels, histopathological and clastogenic damage. It also modulated biochemical indices, inflammatory markers, and hematological parameters. These results collectively indicated that the A. vera gel extract offers protection against whole-body X-ray exposure by virtue of its antioxidant, anti-inflammatory and anti-apoptotic potential.

Radioprotective effect of grape seed extract against gamma irradiation in mouse bone marrow cells.

INTRODUCTION: Ionizing radiations produce free radicals which are often responsible for DNA damage or cell death. Grape seed extract (GSE) is a natural compound having an antioxidant that protects DNA, lipids, and proteins from free radical damages. In this study, radioprotective effect of the GSE has been investigated in mouse bone marrow cells using micronucleus test. MATERIALS AND METHODS: Four groups of mice were investigated in this study: Mice in Group 1 were subjected to injection of distilled water with no irradiation. Mice in Group 2 were exposed to 3 Gy gamma radiation after the injection of distillated water. Mice in Group 3 were injected with 200 mg/kg of the GSE without any irradiation. In another group, mice were exposed to three gray gamma irradiation after the injection of GSE. Animals were killed, and slides were prepared from the bone marrow cells 24 h after irradiation. The slides were stained with May Grunwald-Giemsa method and analyzed microscopically. The frequency of the micronucleated polychromatic erythrocytes (MnPCEs), micronucleated normochromatic erythrocyte (MnNCEs), and polychromatic erythrocyte/polychromatic erythrocyte + normochromatic erythrocyte (PCE/PCE + NCE) ratios was calculated. RESULTS: Injection of GSE significantly decreased the frequency of MnPCEs (P < 0.0001) and MnNCEs (P < 0.05) and increased the ratio of PCE/PCE + NCE (P < 0.0001) compared to the irradiated control group. DISCUSSION AND CONCLUSIONS: GSE could reduce clastogenic and cytotoxic effects of gamma irradiation in mice bone marrow cells; therefore, it can be concluded that the GSE is a herbal compound with radioprotective effects against gamma irradiation. Free radical scavenging and the antioxidant effects of the GSE probably are responsible mechanisms for the GSE radioprotective effects.

The effect of lycopene supplementation on radiation-induced micronuclei in mice reticulocytes in vivo.

Lycopene (LYC) is a natural pigment present in tomatoes and other red fruits and vegetables including red carrots, red peppers, watermelons, pink grapefruits, apricots, pink guavas, and papaya. There is some evidence that LYC may provide protection against mutations induced by ionizing radiation. The study aimed to investigate whether the genetic material of reticulocytes (RET) could be protected from radiation-induced damage by LYC. Mice were treated with LYC [0.15 mg/kg bodyweight (bw), 0.30 mg/kg bw], acute and fractionated irradiation (0.5 Gy, 1 Gy applied daily), or with both agents (0.5 Gy + 0.15 mg/kg bw LYC, 0.5 Gy + 0.30 mg/kg bw LYC, 1 Gy + 0.15 mg/kg bw LYC, 1 Gy + 0.30 mg/kg LYC). LYC supplementation was started at 24 h or 1 week after the first irradiation. Irradiation significantly enhanced the frequency of micronuclei (MN) in RET. LYC treatment at a dose of 0.15 mg/kg bw 24 h after starting fractionated radiation at 1 Gy significantly decreased (41-68%, p < 0.0125) the level of MN in peripheral blood and bone marrow RET. LYC supplementation at 0.30 mg/kg bw did not significantly alter the frequency of MN in peripheral blood, but significantly increased the frequency of bone marrow RET MN. LYC treatment on day 8 following the first radiation exposure showed results similar (92-117%, p > 0.24) to those obtained with irradiation alone. Lycopene may act as a radiomitigator but must be administered at low doses and as soon as possible after irradiation. Contrary, combined exposure with high doses of irradiation and LYC may enhance the mutagenic effect of irradiation.

In Vitro Anti-proliferative Activity and Mechanism of Action of Anemone nemorosa.

Anemone nemorosa is part of the Ranunculaceae genus Anemone (order Ranunculales) which comprises more than 150 species. Various parts of the plant have been used for the treatment of numerous medical conditions such as headaches, tertian agues, rheumatic gout, leprosy, lethargy, eye inflammation as well as malignant and corroding ulcers. The Anemone plants have been found to contain various medicinal compounds with anti-cancer, immunomodulatory, anti-inflammatory, anti-oxidant and anti-microbial activities. To date there has been no reported evidence of its use in the treatment of cancer. However, due to the reported abundance of saponins which usually exert anti-cancer activity via cell cycle arrest and the induction of apoptosis, we investigated the mode of cell death induced by an aqueous A. nemorosa extract by using HeLa cervical cancer cells. Cisplatin was used as a positive control. With a 50% inhibitory concentration (IC50) of 20.33 ± 2.480 µg/mL, treatment with A. nemorosa yielded a delay in the early mitosis phase of the cell cycle. Apoptosis was confirmed through fluorescent staining with annexin V-FITC. Apoptosis was more evident with A. nemorosa treatment compared to the positive control after 24 and 48 h. Tetramethylrhodamine ethyl ester staining showed a decrease in mitochondrial membrane potential at 24 and 48 h. The results obtained imply that A. nemorosa may have potential anti-proliferative properties.

Influence of Land Use and Cover on Toxicogenetic Potential of Surface Water from Central-West Brazilian Rivers.

The objective of this study was to evaluate toxicogenetic potential of surface water samples from rivers of center-west Brazil and analyze the influence of land use and cover and physicochemical parameters in genetic damage. Samples were collected during winter (June) and summer (November) at sampling sites from Dourados and Brilhante Rivers (Mato Grosso do Sul/Brazil). The toxicogenetic variables, including chromosomal alterations, micronuclei, and mitotic index, were analyzed in meristematic cells of Allium cepa; and micronuclei, nuclear abnormalities, and DNA strand breaks (arbitrary units, AUT) were analyzed in erythrocytes of Astyanax lacustris. The rivers presented physicochemical values outside the Brazilian laws, which can be a characteristic of human pollution (domestic sewage and local agriculture). The results of A. cepa test suggest that the water samples from Dourados and Brilhante rivers exerted significant (p < 0.05) cytotoxic and genotoxic effects, in both periods of collection, especially alterations in mitotic index. In blood cells of A. lacustris, genotoxic effect of the water samples from the rivers also was observed as significant nuclear abnormalities, DNA breaks (UAT), in both sampling periods, compared with the negative control. Spearman correlation analyses revealed that data of land use and cover and physicochemical parameters were statistically correlated with DNA damages in bioassays. This study demonstrates toxicogenetic potential of water samples from Dourados and Brilhante rivers; furthermore, the type of land use and land cover and physicochemical parameters were revealed to have influence on toxicogenetic damage.