Phenotypic malignant changes and untargeted lipidomic analysis of long-term exposed prostate cancer cells to endocrine disruptors

Bedia, Carmen; Dalmau, Núria; Jaumot, Joaquim; Tauler, Romà

doi:10.1016/j.envres.2015.03.014

Cited by 41 publications

(41 citation statements)

References 67 publications

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“…Environmental omics consists of the characterization, quantification and study of the variation of biological molecules of an organism when exposed to an environmental stress. The most used techniques for this purpose, HPLC‐MS, GC‐MS, immunoassays, NMR, and so on , are usually destructive techniques. In this work, hyperspectral images (HSI) are used because they allow preserving the natural morphology of the sample and provide spatial and chemical information.…”

Section: Introductionmentioning

confidence: 99%

Combining hyperspectral imaging and chemometrics to assess and interpret the effects of environmental stressors on zebrafish eye images at tissue level

Olmos

Marro

Loza-Álvarez

et al. 2017

Journal of Biophotonics

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Changes on an organism by the exposure to environmental stressors may be characterized by hyperspectral images (HSI), which preserve the morphology of biological samples, and suitable chemometric tools. The approach proposed allows assessing and interpreting the effect of contaminant exposure on heterogeneous biological samples monitored by HSI at specific tissue levels. In this work, the model example used consists of the study of the effect of the exposure of chlorpyrifos-oxon on zebrafish tissues. To assess this effect, unmixing of the biological sample images followed by tissue-specific classification models based on the unmixed spectral signatures is proposed. Unmixing and classification are performed by multivariate curve resolution-alternating least squares (MCR-ALS) and partial least squares-discriminant analysis (PLS-DA), respectively. Crucial aspects of the approach are: (1) the simultaneous MCR-ALS analysis of all images from 1 population to take into account biological variability and provide reliable tissue spectral signatures, and (2) the use of resolved spectral signatures from control and exposed populations obtained from resampling of pixel subsets analyzed by MCR-ALS multiset analysis as information for the tissue-specific PLS-DA classification models. Classification results diagnose the presence of a significant effect and identify the spectral regions at a tissue level responsible for the biological change.

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Section: Introductionmentioning

confidence: 99%

Combining hyperspectral imaging and chemometrics to assess and interpret the effects of environmental stressors on zebrafish eye images at tissue level

Olmos

Marro

Loza-Álvarez

et al. 2017

Journal of Biophotonics

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“…Parabens, a preservative in many cosmetic products, has been found to be in very high levels in 20 human breast cancer specimens. Chemicals such as bisphenol A (BPA), phthalates, perchlorate, atrazine and others have been so classified and linked to breast [54] and prostate [55] cancer. Whether these or other chemicals are linked to estrogen adduct formation is unknown.…”

Section: Resultsmentioning

confidence: 99%

Estrogen Metabolites in the Etiology of Hormone Related Cancers: Possible Role of Anti-Oxidants in Prevention

Westbrock¹

2017

EMIJ

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The goal of this review is to demonstrate the role of metabolic variations in estrogen metabolism and polymorphisms in enzymatic control in the oncogenesis of breast and prostate cancer and Parkinsonism. Further biochemical associations with these cancers are demonstrated. The evidence for interference of oncogenic metabolites by certain anti-oxidants is reviewed. The role of endogenous hormones particularly estrogens in the etiology of several cancers has been postulated for several decades. Benzene has long been associated with leukemia. The benzene ring which includes estrogens, benzene and dopamine are metabolized to orthoquinones which are highly electrophilic and have been shown to be depurinating to DNA. These metabolites are known as estrogen adducts (EA). Estrogen is metabolized in steps involving formation of hydroxyl-estrogens further oxidized by CYP 450 enzymes or peroxidases or by catechol o methyl transferase, and finally by glutathione. In vivo studies demonstrate induction of altered DNA due to purine base knockouts leading to malignant transformation in MC-10 mouse cell lines. Further evidence reveals these changes are not estrogen receptor dependent. Statistically higher urinary levels of EAs have been demonstrated in women with a history of breast cancer and that of men with prostate cancer and lymphoma, as well as in malignant human breast epithelial tissue. In a genetic population of high risk cancers, manifested by BRCA 1 and 2 alterations, DNA double stranded breaks are increased when mice cells are incubated with EAs. BRCA mutations are responsible for induction of substrate metabolites 2-OH E2 and 4 OH E2 by failure of control of cytochrome P450 enzymes (aromatizes) as well as inhibition of quinone oxoreductase which reduces estrogen quinones to lessen formation of EAs. Adducts have an important role in neurotransmitter metabolism, for example in the formation of dopamine quinone DNA adducts. Loss of dopamine in the substantia nigra and metabolic changes in dopamine metabolism may have a role in the pathophysiology of Parkinson's disease. At lower pH ranges dopamine (DA) quinone is metabolized to lead to increasing competitive increase in electrophilic attraction to nucleotide adducts DA-6-N3 Ade and DA 6-N7 Gua which lead to mutagenesis and degeneration in cells of the subsantia nigra. Further research has demonstrated that antioxidants, resveratrol and N-acetyl cysteine (NAc) inhibit formation of EAs in cultured mammary tissue of MC-10 mice, by enhancement of quinone reductase and inhibition of attachment of quinones to DNA purines through glutathione induction. In the case of DA metabolism, reduction of quinone nucleotide activity was demonstrated with the use of lipoic acid, NAc, melatonin and resveratrol. Further clinical trials and epidemiologic studies in humans with described cancers and Parkinson disease are necessary to define these models and prevention in the future.

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“…Cyanobacteria cultures were centrifuged (5000 rpm, 20 min, 4°C) and the supernatants were discarded to recover cell pellets. The extraction has been performed as previously described [19]. Briefly, 100 μL of Mili-Q water was added to the cyanobacteria pellets and the suspension was transferred to borosilicate glass tubes.…”

Section: Lipid Extractionmentioning

confidence: 99%

“…MCR-ALS has been applied to the resolution of elution/concentration and mass spectra profiles for the different components existing in complex cell lipid mixtures analyzed by chromatographic methods [14]. Recently, it has also been applied successfully to resolve complex omics profiling problems, such as in lipidomics [18,19] and metabolomics [20] studies.…”

Section: Introductionmentioning

confidence: 99%

“…Multivariate curve resolution alternating least squares (MCR-ALS) is a chemometric tool applied to resolve multicomponent responses from unknown unresolved mixtures [16][17][18][19]. MCR-ALS has been applied to the resolution of elution/concentration and mass spectra profiles for the different components existing in complex cell lipid mixtures analyzed by chromatographic methods [14].…”

Section: Introductionmentioning

confidence: 99%

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Assessment of the effects of As(III) treatment on cyanobacteria lipidomic profiles by LC-MS and MCR-ALS

et al. 2016

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Cyanobacteria are a group of photosynthetic, nitrogen-fixing bacteria present in a wide variety of habitats such as freshwater, marine, and terrestrial ecosystems. In this work, the effects of As(III), a major toxic environmental pollutant, on the lipidomic profiles of two cyanobacteria species (Anabaena and Planktothrix agardhii) were assessed by means of a recently proposed method based on the concept of regions of interest (ROI) in liquid chromatography mass spectroscopy (LC-MS) together with multivariate curve resolution alternating least squares (MCR-ALS). Cyanobacteria were exposed to two concentrations of As(III) for a week, and lipid extracts were analyzed by ultrahigh-performance liquid chromatography/time-of-flight mass spectrometry in full scan mode. The data obtained were compressed by means of the ROI strategy, and the resulting LC-MS data sets were analyzed by the MCR-ALS method. Comparison of profile peak areas resolved by MCR-ALS in control and exposed samples allowed the discrimination of lipids whose concentrations were changed due to As(III) treatment. The tentative identification of these lipids revealed an important reduction of the levels of some galactolipids such as monogalactosyldiacylglycerol, the pigment chlorophyll a and its degradation product, pheophytin a, as well as carotene compounds such as 3-hydroxycarotene and carotene-3,3'-dione, all of these compounds being essential in the photosynthetic process. These results suggested that As(III) induced important changes in the composition of lipids of cyanobacteria, which were able to compromise their energy production processes. Graphical abstract Steps of the proposed LC-MS + MCR-ALS procedure.

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Phenotypic malignant changes and untargeted lipidomic analysis of long-term exposed prostate cancer cells to endocrine disruptors

Cited by 41 publications

References 67 publications

Combining hyperspectral imaging and chemometrics to assess and interpret the effects of environmental stressors on zebrafish eye images at tissue level

Combining hyperspectral imaging and chemometrics to assess and interpret the effects of environmental stressors on zebrafish eye images at tissue level

Estrogen Metabolites in the Etiology of Hormone Related Cancers: Possible Role of Anti-Oxidants in Prevention

Assessment of the effects of As(III) treatment on cyanobacteria lipidomic profiles by LC-MS and MCR-ALS

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