Geosmin induces genomic instability in the mammalian cell microplate-based comet assay.

Geosmin (GEO) (trans-1,10-dimethyl-trans-9-decalol) is a metabolite that renders earthy and musty taste and odor to water. Data of GEO genotoxicity on mammalian cells are scarce in the literature. Thus, the present study assessed the genotoxicity of GEO on Chinese hamster ovary (CHO) cells in the microplate-based comet assay. The percent of tail DNA (tail intensity (TI)), tail moment (TM), and tail length (TL) were used as parameters for DNA damage assessment. The results demonstrated that concentrations of GEO of 30 and 60 µg/mL were genotoxic to CHO cells after 4- and 24-h exposure periods, in all parameters evaluated, such as TI, TM, and TL. Additionally, GEO 15 µg/mL was genotoxic in the three parameters only in the 24-h exposure time. The same was observed for GEO 7.5 µg/mL, which induced significant DNA damage observed as TI in the 24-h treatment. The results present evidence that exposure to GEO may be associated with genomic instability in mammalian cells.

Agents of earthy-musty taste and odor in water: evaluation of cytotoxicity, genotoxicity and toxicogenomics.

Considering the limited number of studies on the biological effects on human health of cyanobacterial compounds that cause taste and odor, the present study assessed the cytotoxic and genotoxic potentials of 2-methylisoborneol (2-MIB) and geosmin (GEO) using the MTT assay and the in vitro comet and cytokinesis-block micronucleus (CBMN-Cyt) assays in human HepG2 cells. The toxicogenomics of genes responsive to DNA damage and metabolization by the exposure of cells to 2-MIB and GEO were also investigated. The results showed that concentrations of 2-MIB and GEO above 100 and 75 µg/mL, respectively, were cytotoxic to HepG2 cells. Doses of 2-MIB (12.5, 25, 50, 75 and 100 µg/mL) and GEO (12.5, 25, 50, and 75 µg/mL) were unable to induce neither DNA damage nor events associated with chromosomal instability. Similarly, no concentration of each compound induced increments in the expression of CDKN1A, GADD45α, MDM2 and TP53 DNA damage responsive genes as well as in CYP1A1 and CYP1A2 metabolizing genes. Although cytotoxicity was observed, concentrations that caused it are much higher than those expected to occur in aquatic environments. Thus, environmentally relevant concentrations of both compounds are not expected to exhibit cytotoxicity or genotoxicity to humans.

Sudan dyes: are they dangerous for human health?

Azo and diazo compounds include Sudan dyes, which were widely used in industry. Although they are not permitted in food, they had been found contaminating different food products and their presence is investigated regularly (since 2003) in these products. Sudan III, as well as Sudan Black B, was included in different laboratory techniques for tissue ceroid and lipofucsin analysis and blood-cell staining. Also, Sudan Black B has been recently included in in vivo evaluations in human beings (through oral intake), and Sudan III is still allowed in cosmetics. These azo dyes were metabolized to possible carcinogenic colorless amines, both in the liver of mammalians and by the micro flora present in human skin and the gastrointestinal tract. Both human and laboratory animal cytochrome P450s (CYPs) were able to oxidize Sudan I, whereas Sudan III modified CYP activities. In vitro genotoxic effects were reported for Sudan I, and some DNA adducts formed through exposure to its metabolites were identified. Sudan I was also found to be carcinogenic in the rat, but not in the mouse. The aim of the present review is to put together the most relevant information concerning Sudan dye uses and toxicity to provide some tools for the identification of the risk they represent for human health.

Chemical constituents of Papulaspora immersa, an endophyte from Smallanthus sonchifolius (Asteraceae), and their cytotoxic activity.

Papulaspora immersa H. H. Hotson was isolated from roots and leaves of Smallanthus sonchifolius (Poepp. and Endl.) H. Rob. (Asteraceae), traditionally known as Yacon. The fungus was cultured in rice, and, from the AcOEt fraction, 14 compounds were isolated. Among them, (22E,24R)-8,14-epoxyergosta-4,22-diene-3,6-dione (4), 2,3-epoxy-1,2,3,4-tetrahydronaphthalene-c-1,c-4,8-triol (10), and the chromone papulasporin (13) were new secondary metabolites. The spectral data of the known natural products were compared with the literature data, and their structures were established as the (24R)-stigmast-4-en-3-one (1), 24-methylenecycloartan-3ß-ol (2), (22E,24R)-ergosta-4,6,8(14),22-tetraen-3-one (3), (-)-(3R,4R)-4-hydroxymellein (5), (-)-(3R)-5-hydroxymellein (6), 6,8-dihydroxy-3-methylisocoumarin (7), (-)-(4S)-4,8-dihydroxy-α-tetralone (8), naphthalene-1,8-diol (9), 6,7,8-trihydroxy-3-methylisocoumarin (11), 7-hydroxy-2,5-dimethylchromone (12), and tyrosol (14). Compound 4 showed the highest cytotoxic activity against the human tumor cell lines MDA-MB435 (melanoma), HCT-8 (colon), SF295 (glioblastoma), and HL-60 (promyelocytic leukemia), with IC50 values of 3.3, 14.7, 5.0 and 1.6 µM, respectively. Strong synergistic effects were also observed with compound 5 and some of the isolated steroidal compounds.

Influences of phenolic compounds on citric acid productivity by Aspergillus niger in stirred fermentor

Influences of phenol, alpha-naphtol and beta-naphtol, which are toxic chemicals, on citric acid biosynthesis and biomass in the artificial culture setting of Aspergillus niger using batch fermenter are examined in the most favorable fermentation conditions, and a model is proposed. Addition of certain concentrations of phenol, alpha-naphtol and beta-naphtol to the culture increases the citric acid production. According to this model, maximum citric acid concentration is 48.3 g L-1 in a culture that does not contain any toxic chemicals, whereas the maximum concentrations obtained in cultures containing 25 mg L-1 phenol, 25 mg L-1 alpha-naphtol and 15 mg L-1 beta-naphtol are 62.5 g L-1, 78.1 g L-1 and 86.0 g L-1, respectively. Moreover, addition of toxic chemicals to the culture reduces fermentation time by 24 hrs.

Mutagenic and cytotoxic effect of planifolin: a naphthopyranone dimer isolated from Paepalanthus planifolius.

A naphthopyranone dimer, named planifolin, was isolated from a methylene chloride extract of the capitula of Paepalanthus planifolius Koern. The molecule (C(31)H(26)O(10)) appeared to be made up of two monomeric portions, semi-vioxanthin and paepalantine (an isocoumarin), linked by an ether bond, and it may possess several kinds of biological activity that can be related to its polyphenolic structure. Short-term tests that detect genetic damage can afford the information needed to evaluate carcinogenic risks of chemicals to humans. The Ames test, recommended for testing the mutagenicity of chemical compounds with potential pharmacological application, was used in the present study. The mutagenic activity was evaluated in Salmonella typhimurium strains TA100, TA98, TA102 and TA97a and the cytotoxic effect in McCoy cells. The in vitro cytotoxicity of planifolin to McCoy cells, tested in microculture with neutral red, showed a significant cytotoxic index (CI(50)) of 12.83 microg/mL. Planifolin showed mutagenic activity for TA100, TA98 and TA97a. The results indicate that this new naphthopyranone dimer causes mutations by substitution and by addition and deletion of bases in the sequence of DNA. Moreover, its mutagenic potential was increased by metabolic activation.

Isoxazolynaphthoquinone effects on the growth of Trypanosoma cruzi

Frente a la necessidad de hallar neuveos fármacos contra el agente etiológico de la enfermedad de Chagas y en base a las propiedades biológicas y terapéuticas de naftoquinonas e isoxazoles, se resolvió estudiar el efecto de tres isoxazolilnaftoquinonas (Fig. 1) sobre el desarrollo del Trypanosoma cruzi in-vitro e in-vivo. Para evaluar la acción de las drogas sobre los epimastigotes se realizaron curvas de crecimiento con distintas concentraciones de 2-hidroxi-N-(3,4-dimetil-5-isoxazolil)-1,4-naftoquinina-4-imina (I), N-(3,4-dimetil-5-isoxazolil)-4-amino-1,2 naftoquinona (II), 2-acetil-N-(3,4-dimetil-5-isoxazolil)-1,4-naftoquinona-imina (III) y Nifurtimox como droga de referencia. Los estudios sobre la forma de tripomastigote se realizaron sobre ratones BALB/c de dos meses de edad, evaluado parasistemia en el día 13 post-infección. Los resultados obtenidos con epimastigotes mostraron que todas las drogas indujeron alteraciones consistentes es disminución de movilidad, vacuolización, pérdida de viabilidad y/o lisis de los parásitos (Fig. 2 y 3). En los tratamientos sobre tripomastigotes los resultados más concluyentes se presentaron con I que produjo una reducción de la parasitemia respecto a los controles no tratados (Fig 4) (AU)

Isoxazolynaphthoquinone effects on the growth of Trypanosoma cruzi

Frente a la necessidad de hallar neuveos fármacos contra el agente etiológico de la enfermedad de Chagas y en base a las propiedades biológicas y terapéuticas de naftoquinonas e isoxazoles, se resolvió estudiar el efecto de tres isoxazolilnaftoquinonas (Fig. 1) sobre el desarrollo del Trypanosoma cruzi in-vitro e in-vivo. Para evaluar la acción de las drogas sobre los epimastigotes se realizaron curvas de crecimiento con distintas concentraciones de 2-hidroxi-N-(3,4-dimetil-5-isoxazolil)-1,4-naftoquinina-4-imina (I), N-(3,4-dimetil-5-isoxazolil)-4-amino-1,2 naftoquinona (II), 2-acetil-N-(3,4-dimetil-5-isoxazolil)-1,4-naftoquinona-imina (III) y Nifurtimox como droga de referencia. Los estudios sobre la forma de tripomastigote se realizaron sobre ratones BALB/c de dos meses de edad, evaluado parasistemia en el día 13 post-infección. Los resultados obtenidos con epimastigotes mostraron que todas las drogas indujeron alteraciones consistentes es disminución de movilidad, vacuolización, pérdida de viabilidad y/o lisis de los parásitos (Fig. 2 y 3). En los tratamientos sobre tripomastigotes los resultados más concluyentes se presentaron con I que produjo una reducción de la parasitemia respecto a los controles no tratados (Fig 4)

Isoxazolylnaphthoquinone effects on the growth of Trypanosoma cruzi.

Knowing the need for new drugs against the etiologic agent of Chagas disease and considering the biological properties of naphthoquinones and isoxazoles, the effect of three isoxazolyl-naphthoquinones on the growth of Trypanosoma cruzi was studied. To evaluate the activity of the compounds on epimastigote forms, growth curves with different concentrations of 2-hydroxi-N-(3,4-dimethyl-5-isoxazolyl)-1,4-naphthoquinone-4 -imine (I), N-(3,4-dimethyl-5-isoxazolyl)-4-amino-1,2-naphthoquinone (II), 2-acetyl-N-(3,4-dimethyl-5-isoxazolyl)-1,4-naphthoquinone-imine (III) and Nifurtimox as reference drug were made. The studies on the trypomastigote form were performed on two month old BALB/c mice, evaluating parasitemia on day 13 post infection. The results obtained with epimastigotes showed that all drugs induced alterations in motility, morphology, viability and/or lysis of parasites. For the treatments on trypomastigotes the best results were obtained with (I) which reduced parasitemia compared to untreated controls.