Mutagenicity of Flavonoids Assayed by Bacterial Reverse Mutation (Ames) Test

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Genotoxicity of polar and apolar extracts obtained from Qualea multiflora and Qualea grandiflora

Ethnopharmacological relevance: The species Qualea grandiflora and Qualea multiflora, which belong to the Vochysiaceae family, are common in the Brazilian savannah (Cerrado biome), and the local inhabitants use these species to treat external ulcers and gastric diseases and as an anti-inflammatory agent. Studies have demonstrated that these plants contain compounds that exhibit pharmacological activities; however, the risks associated with their consumption are not known.Material and methods: In the present study, the mutagenicity of polar and apolar extracts from Qualea grandiflora and Qualea multiflora were assessed by employing the Ames assay with and without metabolic activation. Additionally, phytochemical analyses (HPLC-ESI-IT-MS, HPLC-UV-PDA and GC-IT-MS) were performed to identify the chemical constituents present in these species, including the evaluation of physico-chemical properties, such as polarity or apolarity of the organic compounds, which are related to each fraction obtained. These studies provide important information regarding the biochemical behaviour of these compounds.Results: All extracts exhibited mutagenicity, inducing frameshift mutations and base substitutions in DNA. Phytochemical analysis identified terpenes, ellagic acid derivatives and phytosteroids.Conclusions: The mutagenicity observed might be due to the presence of pentacyclic triterpenes and polyphenols, which are able to generate reactive oxygen species (ROS) and result in the potential to cause DNA damage. The genetic risk identified in this present work shows that special attention should be considered for the use of compounds obtained from these plant species in medicinal treatments. Further studies must be conducted to identify safe therapeutic doses. (C) 2011 Elsevier B.V. All rights reserved.

Mutagenic evaluation and chemical investigation of Byrsonima intermedia A. Juss. leaf extracts

Byrsonima intermedia is a native species of the cerrado formation (tropical American savannah). In Brazil, this plant has been used for the treatment of fever, in ulcers, as a diuretic, as antiasthinatics and in skin infections. Members of the genus Byrsonima (Malpighiaceae) are employed not only in the folk medicine but also as food to make juice, jellies and liquor. The aim of this work was to evaluate the mutagenic effects of Byrsonima intermedia, common name 'murici'. Phytochernical analysis of methanol extract furnished (+)catechin, (-)-epicatechin, quercetin-3-O-beta-D-galactopyranoside, methyl gallate, gallic acid, quercetin-3-O-alpha-L-arabinopyranoside, amentoflavone, quercetin, querceti n-3-O-(2-O-galloyl)-beta-galactopyranoside and quei-eetin-3-O-(2-O-galloyl)-alpha-arabinopyranoside. Methanol, hydromethanol and chloroform extracts were evaluated in inutagenic assay with Salmonella typhimurium (Ames test) and mice (Micronucleus test). The methanolic extract presented signs of mutagenic activity for the strains TA98 and TA100 in the Ames assay. Mutagenicity was not observed in vivo. (c) 2007 Elsevier B.V.. All rights reserved.

Qualea parviflora Mart.: An integrative study to validate the gastroprotective, antidiarrheal, antihemorragic and mutagenic action

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Byrsonima fagifolia: An integrative study to validate the gastroprotective, healing, antidiarrheal, antimicrobial and mutagenic action

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Mutagenicidade de duas espécies do gěnero Alchornea avaliadas através de ensaios com Salmonella microssomo e teste do micronúcleo

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Estudo químico e biológico de plantas da família Eriocaulaceae

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Does the gastroprotective action of a medicinal plant ensure healing effects? An integrative study of the biological effects of Serjania marginata Casar. (Sapindaceae) in rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

INACTIVATION OF MUTAGENIC DRUGS AND THEIR METABOLITES IN THE URINE OF PATIENTS ADMINISTERED ANTINEOPLASTIC THERAPY

Urines from patients administered mutagenic antineoplastic drugs were significantly mutagenic in the Ames assay, and hence may pose a genotoxic hazard to hospital personnel or family members caring for the patient. The urines were tested for mutagenicity in several different strains of Salmonella typhimurium that were uvr positive or negative (TA98, TA100, TA102, UTH8413, UTH8414). The urines were fractionated by high pressure liquid chromatography (HPLC) and the fractions assayed for mutagenicity in the strains in which the whole urine was mutagenic. Only fractions of urines containing the parent compound (cisplatin, doxorubicin, or mitomycin) were mutagenic; no other fraction showed significant mutagenicity. However, urine containing cyclophosphamide had two fractions that were mutagenic. One fraction, the fraction containing cyclophosphamide, required metabolic activation for mutagenicity. The other fraction did not require activation for mutagenicity.^ The chemical and mutagenic stability of these urines at room temperature was assayed over a 14 day period. The parent compound degraded within the first seven days, but the urines remained mutagenic. Cis-platinum was chemically stable in the urine; however, the urine decreased in mutagenicity. The decrease was probably the result of stable ligands binding to the platinum.^ Inactivation methods were developed to reduce the genotoxic hazard. Urine containing cisplatin was inactivated by complexing the cisplatin with diethyldithiocarbamate (DDTC). Oxidation with NaOCl of urines containing mitomycin and doxorubicin (sodium thiosulfate must be added to the doxorubicin urine) results in mutagenic inactivation. Inactivation of urine containing cyclophosphamide requires oxidation with alkaline potassium permaganate and trapping of active degradation products with sodium thiosulfate. Urines containing these drugs can be inactivated, but not always by the same method that inactivates the drug alone in solution. Therefore, in the future development of inactivation methods, both chemical and mutagenic assays are necessary to determine effectiveness. Methods of inactivation of mutagenic excreta developed in this study are both effective and practical. ^

Differential Toxicity of Disperse Red 1 and Disperse Red 13 in the Ames Test, HepG2 Cytotoxicity Assay, and Daphnia Acute Toxicity Test

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Study of Salmonella typhimurium mutagenicity assay of (E)-piplartine by the Ames test

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Estrogenic and mutagenic activities of crotalaria pallida measured by recombinant yeast assay and ames test

Background: Crotalaria pallida Ailton is a plant belonging to the Fabaceae family, popularly known as rattle or rattlesnake and used in traditional medicine to treat swelling of the joints and as a vermifuge. Previous pharmacological studies have also reported anti-inflammatory, antimicrobial and antifungal activities. Nevertheless, scientific information regarding this species is scarce, and there are no reports related to its possible estrogenic and mutagenic effects. Thus, the purpose of the present study was to investigate the estrogenic potential of C. pallida leaves by means of the Recombinant Yeast Assay (RYA), seeking an alternative for estrogen replacement therapy during menopause; and to reflect on the safe use of natural products to assess the mutagenic activity of the crude extract from C. pallida leaves, the dichloromethane fraction and stigmasterol by means of the Ames test.Methods: The recombinant yeast assay with the strain BY4741 of Saccharomyces cerevisiae, was performed with the ethanolic extract, dichloromethane fraction and stigmasterol isolated from the leaves of C. pallida. Mutagenic activity was evaluated by the Salmonella/microsome assay (Ames test), using the Salmonella typhimurium tester strains TA100, TA98, TA97 and TA102, with (+S9) and without (-S9) metabolization, by the preincubation method.Results: All samples showed estrogenic activity, mainly stigmasterol. The ethanolic extract from C. pallida leaves showed mutagenic activity in the TA98 strain (-S9), whereas dichloromethane fraction and stigmasterol were found devoid of activity.Conclusion: Considering the excellent estrogenic activity performed by stigmasterol in the RYA associated with the absence of mutagenic activity when evaluated by the Ames test, stigmasterol becomes a strong candidate to be used in hormone replacement therapy during menopause. © 2013 Boldrin et al.; licensee BioMed Central Ltd.

Study of Salmonella typhimurium mutagenicity assay of (Z)-piplartine by the Ames test

Processo FAPESP

Rapid transfection assay for screening mutagens and carcinogens

Testing for mutagenicity and carcinogenicity has become an integral part of the toxicological evaluation of drugs and chemicals. Standard carcinogenicity tests in vivo require both large numbers of animals and prolonged experiments. To circumvent these problems, several rapid tests have been developed for preliminary screening of mutagens and carcinogens in vitro. Ames and his associates, the first to develop a mutation test, used mutant strains of Salmonella typhimurium [1]. Mutation tests with Escherichia coli, Bacillus subtilis, Neurospora crassa and Saccharomyces cerevisiae, and DNA-repair tests with E. coli and B. subtilis, have been developed. Cytogenetic assays, in vivo as well as in vitro, in both plant and animal systems, are also used to detect potential mutagens and carcinogens. Transfection is inhibited by base mutation, cleavage of DNA, loss of cohesive ends, interaction with histones, spermidine, nalidixic acid, etc. [3]. The efficiency of transfection is affected by temperature, DNA structure and the condition of the competence of the recipient cells [3]. Transfection assays with phages MS: RNA and ~i, x 174-DNA have been reported [15]. A fast and easy transfection assay using colitis bacteriophage DNA is reported in this communication.

A preliminary characterization of the mutagenicity of atmospheric particulate matter collected during sugar cane harvesting using the Salmonella/microsome microsuspension assay

During sugar cane harvesting season, which occurs from May to November of each year, the crops are burnt, cut, and transported to the mills. There are reports showing that mutagenic activity and PAH content increase during harvesting season in some areas of Sao Paulo State in comparison with nonharvesting periods. The objective of this work was to preliminarily characterize the mutagenic activity of the total organic extracts as well as corresponding organic fractions of airborne particulate matter (PM) collected twice from two cities, Araraquara (ARQ) and Piracicaba (PRB), during sugar cane harvesting season using the Salmonella/microsome microssuspension assay. One sample collected in Sao Paulo metropolitan area was also included. The mutagenicity of the total extracts ranged from 55 to 320 revertants per cubic meter without the addition of S9 and from not detected to 57 revertants per cubic meter in the presence of S9 in areas with sugar cane plantations. Of the three fractions analyzed, the most polar ones (nitro and oxy) were the most potent. A comparison of the response of TA98 with YG1041 and the increased potencies without S9 indicated that nitro compounds are causing the observed effect. More studies are necessary to verify the sources of the mutagenic activity such as burning of vegetal biomass and combustion of heavy duty vehicles used to transport the sugar cane to the mills. The Salmonella/microsome assay can be an important tool to monitor the atmosphere for mutagenicity during sugar cane harvesting season.