Showing papers on "Ames test published in 2010"

Alternatives to the carcinogenicity bioassay: in silico methods, and the in vitro and in vivo mutagenicity assays.

Abstract: Importance of the field: Carcinogenicity and mutagenicity are toxicological end points posing considerable concern for human health. Due to the cost in animal lives, time and money, alternative approaches to the rodent bioassay were designed based on: i) identification of mutations and ii) structure–activity relationships.Areas covered in this review: Evidence on i) and ii) is summarized, covering 4 decades (1971 – 2010).What the reader will gain: A comprehensive, state-of-the-art perspective on alternatives to the carcinogenicity bioassay.Take home message: Research to develop mutagenicity-based tests to predict carcinogenicity has generated useful results only for a limited area of the chemical space, that is, for the DNA-reactive chemicals (able to induce cancer, together with a wide spectrum of mutations). The most predictive mutagenicity-based assay is the Ames test. For non-DNA-reactive chemicals, that are Ames-negative and mutagenic in other in vitro assays (e.g., clastogenicity), no correlation wi...

Mutagenic and antimutagenic effects of hexane extract of some Astragalus species grown in the eastern Anatolia region of Turkey.

Abstract: Medical plants and their various extracts have been occasionally used in the treatment of many diseases. Astragalus is one of those medical plants and it has several biological activities. In the present study, the hexane extracts of six Astragalus species, which are grown in the eastern Anatolia region of Turkey, were isolated, and their mutagenic and antimutagenic properties were investigated by using Salmonella typhimurium TA1535, TA1537 and Escherichia coli WP2uvrA tester strains at 0.05, 0.5 and 5 microg/plate concentrations. Known mutagens sodium azide (NaN(3)), 9-Aminoacridine (9-AA) and N-Methyl-N'-nitro-N-nitrosoguanidine (MNNG) were used to determine antimutagenic properties of hexane extracts. The results showed that all hexane extracts, investigated in the present study, can be considered genotoxically safe because they do not have mutagenic activity at the tested concentrations. But, a great many of them have antimutagenic activity against 9-Aminoacridine known as a model intercalator agent. The inhibition rates obtained from the antimutagenicity assays ranged from 27.51% (A. macrocephalus--0.05 microg/plate) to 54.39% (A. galegiformis--5 microg/plate). These activities are valuable toward an extension of the employ of these drugs as new phytotherapeutic or preservative ingredients.

Analysis of published data for top concentration considerations in mammalian cell genotoxicity testing.

Abstract: The ability of the in vitro mammalian cell tests currently used to identify genotoxins has been shown to be limited by a high rate of false-positive results, triggering further unnecessary testing in vivo. During an European Centre for the Validation of Alternative Methods workshop on how to improve the specificity of these assays, testing at high concentrations was identified as one possible source of false positives. Thus far, Organisation for Economic Co-operation and Development genotoxicity test guidelines have required testing of chemicals using mammalian cells in vitro should be undertaken to concentrations as high as 10 mM (5000 mg/ml). Recently, a draft revision of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use genotoxicity test guidelines has recommended that testing concentrations should be reduced to 1 mM (500 mg/ml). To assess the impact that this lowering would have on the outcome of in vitro genotoxicity testing, we established a database of 384 chemicals classified as rodent carcinogens and reported Ames test results and the test concentrations that produced positive results in the mouse lymphoma assay (MLA), in vitro chromosome aberration (CA) assay and in vitro micronucleus test. Genotoxicity testing results were illustrated for 229 and 338 compounds in the MLA and in vitro CA assay, respectively. Of these test compounds, 62.5% produced positive results in the MLA, of which 20.3% required testing between 1 and 10 mM. A total of 58.0% produced positive results in in vitro CA assays, of which 25.0% required testing between 1 and 10 mM. If the testing concentration limit for mammalian cell assays was reduced to 1 mM, 24 (6.25%) potential carcinogens would not be detected in any part of the standard in vitro genotoxicity test battery (Ames test, MLA and in vitro CA assay). Further re-evaluation and/or retest of these compounds by Kirkland and Fowler [Kirkland, D. and Fowler, P. (2010) Further analysis of Ames-negative rodent carcinogens that are only genotoxic in mammalian cells in vitro at concentrations exceeding 1 mM, including retesting of compounds of concern. Mutagenesis doi:10.1093/mutage/geq041] suggest that the current 10 mM top concentration can be reduced without any loss of sensitivity in detecting rodent carcinogens.

Antimutagenic and anti-oxidant activities of isoflavonoids from Belamcanda chinensis (L.) DC.

Abstract: The isoflavonoid fractions obtained from a methanolic extract of Belamcanda chinensis (L.) DC (syn. Iris domestica Goldblatt & Mabb.) rhizomes inhibited the chemically induced mutations in Salmonella typhimurium TA98 and TA100 in the Ames test. We have studied direct mutagenesis induced by N-nitroquinoline, and indirect mutation induction caused by metabolically activated 2-AF. The fractions enriched in isoflavonoids, obtained by sequential liquid-liquid extraction with diethyl ether and butanol, followed by ODS column separation, inhibited indirect mutagenesis in TA98 almost completely. In TA100 the maximum inhibition ranged between 80% and 100% depending on the test fraction. The inhibition of direct mutagenesis was lower, reaching about 50% in TA98 and in TA100, but it was dose-dependent only in the latter strain. Three in vitro anti-oxidant spectrophotometric assays-DPPH free-radical scavenging test, the phosphomolybdenum assay, and the linoleic acid peroxidation assay were also performed to support the process of bioactivity-guided fractionation and to provide more information about the potential mechanisms of action of the herb under study. The isoflavonoid fractions have the capability to scavenge free radicals, to reduce transition-metal ions and to protect polyunsaturated fatty acids from peroxidation. The analysis of the fractions obtained with high-performance liquid chromatography with photodiode-array and mass-spectrometric detection revealed several potentially bioactive isoflavones, either as glycosides or aglycones, depending on the polarity of the solvents used for fractionation. The main compounds were tectoridin and iridin in the glycoside fractions and the aglycones irigenin, tectorigenin, and 5,6,7,3'-tetrahydroxy-4'-methoxyisoflavone. The activities reported here can be regarded to be of additional value when using this plant as a phyto-estrogenic and chemopreventive agent.

Whole cell-ELISA to measure the γH2AX response of six aneugens and eight DNA-damaging chemicals

Abstract: The phosphorylated form of the histone protein H2AX (gammaH2AX) plays a central role in sensing and repairing DNA damage and is a sensitive marker for DNA double-strand breaks (DSB). Although a wide range of genotoxic agents that do not initiate DSB induce gammaH2AX, the range of chemicals that cause H2AX phosphorylation is not clear. We designed a novel, whole cell enzyme-linked immunosorbent assay (cell-ELISA) that can accurately quantify gammaH2AX levels and identify chemical compounds that induce gammaH2AX formation; our novel assay is more convenient than microscopic examination of gammaH2AX foci or flow cytometry. We measured gammaH2AX levels in CHL, CHO and V79 cells exposed to DNA-damaging, non-genotoxic and aneugenic chemicals using the cell-ELISA assay. The cell-ELISA results for the DNA-damaging compounds (methyl methanesulfonate, N-ethyl-N'-nitro-N-nitrosoguanidine, mitomycin C, cisplatin, irinotecan, etoposide, methotrexate and 5-fluorouracil) assayed showed that there was a concentration-dependent increase in gammaH2AX, which was 1.5-fold greater than the negative control; the only exception was a negative response of CHO cells to 5-fluorouracil. None of the 10 non-genotoxic compounds assayed showed similar increases in gammaH2AX and all exhibited concentration-dependent growth inhibition of the cells. The highest levels of gammaH2AX found from treatment with aneugens (vincristine, colcemid, paclitaxel, griseofulvin, 17-allylaminogeldanamycin and CH3310395), which are compounds that cause spindle dysfunction and have no genotoxic activity in the Ames test, were 1.5-fold lower than the negative control. In contrast, mitomycin C and etoposide, which both have aneugenic and DNA-damaging activities, induced a positive response. None of the aneugens caused an increase in gammaH2AX at concentrations that induce micronuclei. The chemical classes that show positive results in the cell-ELISA are different from those that are positive in the Ames or in vitro micronucleus test. By using the cell-ELISA for the level of gammaH2AX, we were able to distinguish DNA-damaging agents from non-genotoxic compounds or aneugens.

Further analysis of Ames-negative rodent carcinogens that are only genotoxic in mammalian cells in vitro at concentrations exceeding 1 mM, including retesting of compounds of concern

Abstract: In the analysis by Parry et al. [Parry, J. M., Parry, E., Phrakonkham, P. and Corvi, R. (2010) Analysis of published data for top concentration considerations in mammalian cell genotoxicity testing. Mutagenesis, 25, 531–538], 24 rodent carcinogens that were negative in the Ames test were identified that were only positive in mammalian cell tests at concentrations between 1 and 10 mM. These carcinogens can be subdivided into four groups as follows: (1) probable non-genotoxic (non-mutagenic) carcinogens, tumour promoters or negative for genotoxicity in vivo (n 5 10); (2) questionable carcinogens (n 5 4); (3) carcinogens with a probable genotoxic mode of action (n 5 5); (4) compounds where carcinogenicity or in vivo genotoxicity is unknown or unclear (n 5 5). It is not expected that in vitro mammalian cell tests should give positive results with Group 1 chemicals. Within Groups 2–4, five chemicals were considered a low priority because they could be detected using modified conditions because genotoxicity was associated with precipitate or pH shifts or because non-standard metabolism was required. The remaining nine chemicals were therefore considered most critical in terms of detection of genotoxic activity in mammalian cells. Daminozide was also included because it may have given positive responses between 1 and 10 mM. Many of the reported studies could have given positive results only at >1 mM because ‘old’ protocols were followed. These 10 chemicals have therefore been retested using modern protocols. Some were negative even up to 10 mM. Others were positive at concentrations 1m M (2 mM 5 202 mg/ml). Low-molecular weight substances may therefore require concentrations >1 mM, but further work is needed. Based on this analysis, it is concluded that the 10 mM upper limit in mammalian cell tests can be lowered without any loss of sensitivity in detecting genotoxic rodent carcinogens. A new limit of 1 mM or 500 mg/ml, whichever is the higher, is proposed.

Assessment of DNA damage induced by extracts, fractions and isolated compounds of Davilla nitida and Davilla elliptica (Dilleniaceae)

Abstract: Davilla nitida and Davilla elliptica (Dilleniaceae) are plants that occur predominantly in the cerrado region of South America. They are used in popular medicine to treat stomach diseases, diarrhea and swelling, particularly of the lymph nodes and testicles. Chemical investigation of these two plant species led to the identification of the compounds myricetin-3-O-α-l-rhamnoside (myricitrin), quercetin-3-O-α-l-rhamnoside (quercitrin), myricetin, quercetin and gallic acid derivatives in the leaves of D. nitida and D. elliptica. Therefore, it was concluded that the two species of Davilla possess qualitatively similar chemical profiles. In the present study, the mutagenic and genotoxic potential of these plants and of their isolated compounds was tested in the Salmonella typhimurium assay (Ames test) with strains TA100, TA98, TA102 and TA97a, in the micronucleus test with peripheral blood cells of mice treated in vivo, and in plasmid DNA to analyze DNA strand-breaks. In the assessment of mutagenic potential by the Ames test, extracts from both plant species and a D. nitida ethyl-acetate fraction induced positive responses. On the other hand, none of the extracts showed genotoxic activity in the mouse cells. In the presence of metal ion, D. nitida and D. elliptica aqueous and ethyl-acetate fractions, as well as their isolated compounds, induced single- and double-strand-breaks in plasmid DNA in a cell-free system.

Anti-mutagenic and pro-apoptotic effects of apigenin on human chronic lymphocytic leukemia cells.

Abstract: Diet can play a vital role in cancer prevention. Nowadays the scientists are looking for food materials which can potentially prevent the cancer occurrence. The purpose of this research is to examine anti-mutagenic and apoptotic effects of apigenin in human lymphoma cells. In present study human chronic lymphocytic leukemia (Eheb cell line) were cultured in RPMI 1640 (Sigma), supplemented with 10% fetal calf serum, penicillin-streptomycin, L-glutamine and incubated at 37 oC for 2 days. In addition cancer cell line was treated by and apigenin and cellular vital capacity was determined by MTT assay. Then effect of apigenin in human lymphoma B cells was examined by flow cytometry techniques. The apigenin was subsequently evaluated in terms of anti-mutagenic properties by a standard reverse mutation assay (Ames test). This was performed with histidine auxotroph strain of Salmonella typhimurium (TA100). Thus, it requires histidine from a foreign supply to ensure its growth. The aforementioned strain gives rise to reverted colonies when exposed to sodium azide as a carcinogen substance. During MTT assay, human chronic lymphocytic leukemia revealed to have a meaningful cell death when compared with controls (P<0.01) Apoptosis was induced suitably after 48 hours by flow cytometry assay. In Ames test apigenin prevented the reverted mutations and the hindrance percent of apigenin was 98.17%.These results have revealed apigenin induced apoptosis in human lymphoma B cells in vitro.

Mutagenicity of two species of the genus Alchornea measured by Salmonella microsome assay and micronucleus test

Abstract: Some species of the plant genus Alchornea (family Euphorbiaceae) are widely used in popular medicine, mainly in South America and in Africa. Several kinds of biological activity have been seen in the species: antioxidant, antifungal, anti-inflammatory, antibacterial, cytotoxic against tumor cell lines and inhibitory to the replication of HIV-1 and HIV-2. In Brazil, the species Alchornea castaneaefolia Willd. A. Juss. and Alchornea glandulosa Poepp. & Endl. are used by the local population to treat rheumatism, arthritis and muscular pains. In view of the popular use of these plants as medicines and the potential risks from their consumption, we assessed the mutagenic potential of chloroform and methanol extracts of the leaves of these plant species, employing the in vivo micronucleus test and the Ames assay. The data obtained showed that the chloroform extracts were not mutagenic. The methanol extract of A. castaneaefolia was mutagenic to strain TA98 of Salmonella typhimurium and the methanol extract of A. glandulosa to strains TA98 and TA97a. The methanol extracts of both species of Alchornea were mutagenic in vivo at the largest dose employed. The probable mutagenic agents involved were the aglycone quercetin and amentoflavone, present in both species.

Genotoxicity and antigenotoxicity evaluation of non-photoactivated hypericin.

Abstract: The potential genotoxicity and antigenotoxicity of non-photoactivated hypericin was investigated in five experimental models. Hypericin was non-mutagenic in the Ames assay, with and without metabolic activation. It did not exert a protective effect against mutagenicity induced by 9-aminoacridine. In a yeast (Saccharomyces cerevisiae) assay, hypericin did not increase the frequency of mitotic crossovers or total aberrants at the ade2 locus, the number of convertants at the trp5 locus, or the number of revertants at the ilv1 locus. In combined application with 4-nitroquinoline-1-oxide, it significantly enhanced the number of revertants at the ilv1 locus at the highest concentration used. Hypericin was not mutagenic in the alga Chlamydomonas reinhardtii. However, in combined application with methyl methane sulfonate, toxicity and mutagenicity were slightly reduced. In a chromosome aberration assay using three mammalian cell lines, hypericin did not alter the frequency of structural chromosome aberrations, and in the DPPH radical scavenging assay, it did not exert any antioxidant effects. Copyright © 2009 John Wiley & Sons, Ltd.

DNA-damaging, mutagenic, and clastogenic activities of gentiopicroside isolated from Cephalaria kotschyi roots.

Abstract: Gentiopicroside (1) is the major secoiridoid glucoside constituent of Cephalaria kotschyi roots. The mutagenicity, DNA-damaging capacities, and clastogenicity of this molecule were evaluated by the Salmonella typhimurium mutagenicity assay (Ames test) on tester strains TA97a, TA98, TA100, and TA102, the alkaline comet assay, and the micronucleus assay on CHO cells. All tests were performed with and without the metabolization mixture, S9 mix. In the Ames test, the mutagenicity of 1 was limited to TA102 without S9 mix (2.3 rev μg−1). The genotoxicity was more evident without S9 mix (0.78 OTMχ2 units μg−1 mL) than with the metabolic mixture (0.16 OTMχ2 units μg−1 mL) with the comet assay. Similarly, the clastogenicity without S9 mix was 0.99 MNC μg−1 mL and 0.38 MNC μg−1 mL with S9 mix in the micronucleus assay. The interaction of 1 with DNA is probably through the involvement of oxidative DNA lesions.

In vitro genotoxicity of polychlorinated butadienes (Cl4–Cl6)

Abstract: Tetrachlorinated butadienes (TetraCBDs), pentachlorinated butadienes (PentaCBDs) and hexachloro-1,3-butadiene (hexachlorobutadiene or HexaCBD) are environmental contaminants that can occur in groundwater and drinking water at specific sites. While some toxicological data exist for HexaCBD, only few or no toxicity data are available for TetraCBDs and PentaCBDs. In view of structural alerts for potential genotoxicity and carcinogenicity, the genotoxicity of these substances was examined in the Salmonella typhimurium mutagenicity assay (Ames test) and in the in vitro chromosome aberration test. All of the tested polychlorinated butadienes induced chromosome aberrations. Such an effect of HexaCBD is reported here for the first time. In addition, 1,1,3,4-TetraCBD and 1,2,3,4-TetraCBD were positive in the Ames test while the other polychlorinated butadienes including HexaCBD were negative. From these findings it is concluded that certain incompletely chlorinated butadienes have a different genotoxic profile than the completely halogenated HexaCBD, which is of relevance for the risk assessment of these compounds.

Evaluation of mutagenic activity of the organo-selenium compound Selol by use of the Salmonella typhimurium mutagenicity assay.

Abstract: We examined the mutagenic activity of the anti-oxidant Selol, an organo-selenium compound, by use of the Salmonella typhimurium mutagenicity assay (Ames test) with strains TA97a, TA98, TA100, TA 1535 and TA102 in the absence and in the presence of metabolic activation with an S9 fraction from Aroclor-induced rat liver. Doses were 330, 500, 1000 and 5000 μg per plate. Selol contains the element selenium (valency, +4) in its structure and it may have chemopreventive and anticancer activity. Selol was found to be non-toxic and non-mutagenic for test doses up to 5% per plate (which designates the declared content of Selenium (+4) as 5000 μg per plate) in all the S. typhimurium strains.

In-vitro mutagenic potential and effect on permeability of co-administered drugs across Caco-2 cell monolayers of Rubus idaeus and its fortified fractions.

Abstract: This study investigated the mutagenic, anti-mutagenic and cytotoxic effects of acetone extract of raspberry, Rubus idaeus L. (v. Ottawa) Rosaceae, and the isolated and characterized ellagitannin and anthocyanin fractions thereof, suitable for food applications. The studied raspberry extract and fractions did not show any mutagenic effects determined in the miniaturized Ames test and were not cytotoxic to Caco-2 cells at the used concentrations. However, the anti-mutagenic properties were changed (i.e. decreased mutagenicity of 2-nitrofluorene in strain TA98, and slightly increased mutagenicity of 2-aminoanthracene in strain TA100) with metabolic activation. Further, their influence on the permeability of co-administered common drugs (ketoprofen, paracetamol, metoprolol and verapamil) across Caco-2 monolayers was evaluated. The apical-to-basolateral permeability of highly permeable verapamil was mostly affected (decreased) during co-administration of the raspberry extract or the ellagitannin fraction. Ketoprofen permeability was decreased by the ellagitannin fraction. Consumption of food rich in phytochemicals, as demonstrated here with chemically characterized raspberry extract and fractions, with well-absorbing drugs would seem to affect the permeability of some of these drugs depending on the components. Thus their effects on the absorption of drugs in-vivo cannot be excluded.

DNA modifications by the omega-3 lipid peroxidation-derived mutagen 4-oxo-2-hexenal in vitro and their analysis in mouse and human DNA.

Abstract: 4-Oxo-2-hexenal (4-OHE), which forms a 2'-deoxyguanosine (dG) adduct in a model lipid peroxidation system, is mutagenic in the Ames test. It is generated by the oxidation of omega-3 fatty acids and is commonly found in dietary fats, such as fish oil, perilla oil, rapeseed oil, and soybean oil. 4-OHE also forms adducts with 2'-deoxyadenosine (dA), 2'-deoxycytidine (dC), and 5-methyl-2'-deoxycytidine (5-Me-dC) in DNA. In this study, we characterized the structures of these adducts in detail. We measured the amounts of 4-OHE-DNA adducts in mouse organs by LC/MS/MS, after 4-OHE was orally administered to mice. The 4-OHE-dA, 4-OHE-dC, 4-OHE-dG, and 4-OHE-5-Me-dC adducts were detected in stomach and intestinal DNA in the range of 0.25-43.71/10(8) bases. After the 4-OHE administration, the amounts of these DNA adducts decreased gradually over 7 days. We also detected 4-OHE-dC in human lung DNA, in the range of 2.6-5.9/10(9) bases. No difference in the 4-OHE adduct levels was detected between smokers and nonsmokers. Our results suggest that 4-OHE-DNA adducts are formed by endogenous as well as environmental lipid peroxides.

Mutagenicity of new lead compounds to treat sickle cell disease symptoms in a Salmonella/microsome assay.

Abstract: A series of phthalimide derivatives planned as drugs candidates to treat the symptoms of sickle cell anemia were evaluated in a mutagenicity test using strains of Salmonella typhimurium TA100 and TA102, without and with addition of S9 mixture, with the aim to identify the best structural requirements for a drug candidate without genotoxic activity. The compounds (1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl nitrate (1); (1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl nitrate (2); 3-(1,3-dioxo-1,3-dihydro-2H-iso-indol-2-yl)benzyl nitrate (3); 4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N-hydroxy-benzenesulfonamide (4); 4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)benzyl nitrate (5) and 2-[4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)phenyl]ethyl nitrate (6) presented mutagenic potency ranging between 0–4,803 revertants/μmol. These results allowed us to propose that a methyl spacer linked to a nitrate ester subunit associated to meta aromatic substitution decreases mutagenicity.

Antimutagenic and Potential Anticarcinogenic Activities of Aloe-Vera Gel and Aqueous Garlic Extract in the Bacterial Reverse Mutation Test (Ames Assay)

Abstract: The study was carried out to verify the potential anticarcinogenic and antimutagenic activity of garlic and aloe-vera. The ability of aqueous garlic extract and Aloe-Vera gel to inhibit mutation in tester strain of Escherichia coli WP2 uvrA was determined in this study. (The tester E. coli tryptophan auxotroph strain was obtained from Yale University U.S.A.). The spontaneous mutation rate of E. coli WP 2 uvrA was determined in the Ames assay to be 2.2 x 10-7. The acridine mutagen showed 333.8% increase of spontaneously reverting colonies of the tester strain. Different concentrations of aqueous garlic extract and aloe-vera gel conferred varying degrees of antimutagenic activities on the tester E. coli WP2 uvrA. Aqueous garlic extract was found to have its highest antimutagenic activity at a concentration of 0.5g/cm3 (the highest concentration tested) with 81.02% reduction in revertant colonies were observed. 0.1g/cm-3 and 0.25g/cm-3 garlic extract produced 72.16% and 74.82% reduction of revertant colonies respectively. Aloe-Vera gel produced 43.6%, 37.2% and 33.68% reduction in revertant colonies at concentration of 0.5ml, 0.2ml and 0.1ml per plate of the E. coli respectively. From the result obtained in this study, garlic has tremendous potential antimutagenic and anticarcinogenic substances.. (Afr. J. Biomed. Res. 10: 275 – 278) Key words : - Oreochromis niloticus, infection, Clinostonum tilapiae, histopathology

Urinary mutagenicity and genotoxic risk in children with psoriasis after therapeutic exposure to polycyclic aromatic hydrocarbons and ultraviolet radiation

Abstract: The Goeckerman regimen (GR) for the treatment of psoriasis comprises dermal application of crude coal tar (polycyclic aromatic hydrocarbons, PAHs) and exposure to ultraviolet radiation (UVR). PAHs and UVR are mutagenic and carcinogenic agents. We evaluated dermal absorption of PAHs as well as the mutagenic and genotoxic effects of GR in 16 children with psoriasis, by determining levels of 1-hydroxypyrene (1-OHP), 1-,2-,3-,4-hydroxyphenanthrene, (1-OHPhe, 2-OHPhe, 3-OHPhe, and 4-OHPhe), urinary mutagenicity (Salmonella mutagenicity assay, Ames test) and numbers of chromosomal aberrations in peripheral lymphocytes (CA), in urine and/or blood, before and after GR. The Psoriasis Area and Severity Index (PASI) score was used to evaluate clinical efficacy of GR. Compared with pre-treatment levels, there were significant increases in urinary concentrations of 1-OHP (p

Absence of mutagenic effects of a particular Symphytum officinale L. liquid extract in the bacterial reverse mutation assay.

Abstract: Comfrey (Symphytum officinale L.) root is traditionally used for the topical treatment of contusions, strains and sprains. Besides allantoin and rosmarinic acid, which are discussed as pharmacologically active principles, the drug contains pyrrolizidine alkaloids (PAs) known for their hepatotoxic, carcinogenic and mutagenic properties. The topical herbal medicinal products Kytta-Salbe f and Kytta-Plasma f contain a PA-free liquid extract from comfrey root as active substance. The aim of this study was to demonstrate the absence of genotoxic effects of this special extract in the bacterial reverse mutation assay (Ames test). Briefly, comfrey root liquid extract was investigated for its ability to induce gene mutations in Salmonella typhimurium strains TA 98, TA 100, TA 102, TA 1535 and TA 1537 with and without metabolic activation using the mammalian microsomal fraction S9 mix. Reference mutagens were used to check the validity of the experiments. Comfrey root fluid extract showed no biologically relevant increases in revertant colony numbers of any of the five tester strains, neither in the presence nor in the absence of metabolic activation. In conclusion, the comfrey root fluid extract contained in Kytta-Salbe f and Kytta-Plasma f was not mutagenic in the bacterial reverse mutation assay.

Mutagenicity of octane and tetrasodium pyrophosphate in bacterial reverse mutation (Ames) test.

Abstract: We investigated the genotoxicities or mutagenicities of 2 chemicals (octane and tetrasodium pyrophosphate) with limited toxicological data in spite of their common usage based on Ames reverse mutation test. In this test, treatment of 2 chemicals at each five dose did not induce mutagenicity in Salmonella typhimurium TA98, TA100, TA1535, TA1537, and in Escherichia coli WP2uvrA with and without metabolic activation. These results indicate that 2 chemicals do not have mutagenic potentials under the conditions examined in each study. Despite these results, it can affect by inducing inhalation, skin or eye contact, ingestion, and have affected central nervous system as a target organ. It is thus necessary to prepare the local exhaust system and personal protective equipments. Based on this study, we suggest that future studies should be directed toward chronic inhalation, carcinogenic test and so on.

Evaluation of Mutagenic Potential of Food Dye (Apple Green)

Abstract: Food dyes are the vital constituents of food enhancing the aesthetic appeal of it by providing different colours. But synthetic dyes contained different heavy metals like lead, mercury, arsenic, copper, nickel, manganese, cobalt etc. which on the other hand are known mutagens/carcinogens. Considering the alarming mutagenic and carcinogenic potential of food dyes, the present study was planned to evaluate the mutagenic effect of apple green, the most widely used food dye, by confectioners in pista burfi, candies, cakes, ice creams, pasteries, jellies and cold drinks. The dye was purchased from local market and was of Ajanta make. This dye is a blend of sodium chloride, tartrazine and brilliant blue. Different concentrations of the dye ranging from 25 μg to 2500 μg/0.1 ml culture were prepared by using sterile double distilled water. The mutagenic effects of prepared extract were estimated employing Ames test using two tester strains TA98 and TA100 of Salmonella typhimurium . It was observed that the dye was moderately mutagenic at higher concentrations in Salmonella strain TA100 and non mutagenic in TA98.