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Humans are routinely exposed to nanoplastics (NPs) in various ways, and this exposure presents a significant health risk. Nevertheless, there remain gaps in our knowledge, particularly in the mechanisms of toxicity of NPs with different surface charges at very low environmental concentrations. Herein, a spectrochemical approach was used to profile the cytotoxicity of NPs with different surface charges in HepG 2 cells. It was found that all three NPs can cause some biomolecular alterations in cells, affecting cellular lipids, proteins, amino acids, and genetic material. Of these, PS and PS-COOH led to a non-linear dose-response, which may be related to a biphasic dose-response, whereas PS-NH 2 led to a linear dose-response with a gradual increase in toxicity with increasing exposure concentration. In addition, the spectroscopic results showed that surface modifications led to cellular biochemical changes and caused adverse biological effects, with PS-NH 2 exhibiting higher toxicity compared to PS or PS-COOH along with an inhibition of cell proliferation. Surprisingly PS-COOH, although considered the least toxic NP, appears to cause DNA damage. Overall, the toxic effects of different surface-modified NPs in cells were detected for the first time by applying spectrochemical techniques, and these findings provide important data towards understanding the emerging widespread environmental pollution of NPs and their effects on humans. [Display omitted] • Biospectroscopy identify the cytotoxicity alterations of nanoparticles at the PPb level • Nanoplastics affect intracellular proteins, lipids, amino acids and genetic material • Aminated nanoparticles led to a linear and positively correlated dose response • Aminated nanoparticles is more toxic than carboxylated or non-functionalized ones [ABSTRACT FROM AUTHOR]

Environmental factors may increase colon cancer (CC) risk. It has been suggested that pesticides could play a significant role in the etiology of this malignancy. As agriculture is one of the mainstays of the Brazilian economy, this country has become the largest pesticides consumer worldwide. The CC burden is also increasing in Brazil. Herein, we examined data from the Brazilian Federal Government to determine whether CC mortality and pesticide consumption may be associated. Database of the Ministry of Health provided CC mortality data in Brazil, while pesticide usage was accessed at the website of Brazilian Institute of Environment and Renewable Natural Resources. The CC mortality in the Brazilian states was calculated as standard mortality rates (SMR). All Bayesian analysis was performed using a Markov chain Monte Carlo method in WinBUGS software. We observed that CC mortality has exhibited a steady increase for more than a decade, which correlated with the amount of sold pesticides in the country. Both observations are concentrated in the Southern and the Southeast regions of Brazil. Although ecological studies like ours have methodological limitations, the current dataset suggests the possibility that pesticide exposure may be a risk factor for CC. It warrants further investigation. [ABSTRACT FROM AUTHOR]

Amphibians are undergoing large population declines in many regions around the world. As environmental pollution from both agricultural and urban sources has been implicated in such declines, there is a need for a biomonitoring approach to study potential impacts on this vulnerable class of organism. This study assessed the use of infrared (IR) spectroscopy as a tool to detect changes in several tissues (liver, muscle, kidney, heart and skin) of late-stage common frog ( Rana temporaria ) tadpoles collected from ponds with differing water quality. Small differences in spectral signatures were revealed between a rural agricultural pond and an urban pond receiving wastewater and landfill run-off; these were limited to the liver and heart, although large differences in body size were apparent, surprisingly with tadpoles from the urban site larger than those from the rural site. Large differences in liver spectra were found between tadpoles from the pesticide and nutrient impacted pond compared to the rural agricultural pond, particularly in regions associated with lipids. Liver mass and hepatosomatic indices were found to be significantly increased in tadpoles from the site impacted by pesticides and trace organic chemicals, suggestive of exposure to environmental contamination. Significant alterations were also found in muscle tissue between tadpoles from these two ponds in regions associated with glycogen, potentially indicative of a stress response. This study highlights the use of IR spectroscopy, a low-cost, rapid and reagent-free technique in the biomonitoring of a class of organisms susceptible to environmental degradation. [ABSTRACT FROM AUTHOR]

Fourier-transform infrared (FTIR) spectroscopy is an emerging technique to detect biochemical alterations in biological tissues, particularly changes due to sub-lethal exposures to environmental contaminants. We have previously shown the potential of attenuated total reflection FTIR (ATR-FTIR) spectroscopy to detect real-time exposure to contaminants in sentinel organisms as well as the potential to relate spectral alterations to the presence of specific environmental agents. In this study based in the Niger Delta (Nigeria), changes occurring in fish tissues as a result of polycyclic aromatic hydrocarbon (PAH) exposure at contaminated sites are compared to the infrared (IR) spectra of the tissues obtained from a relatively pristine site. Multivariate analysis revealed that PAH contamination could be occurring at the pristine site, based on the IR spectra and significant ( P < 0.0001) differences between sites. The study provides evidence of the IR spectroscopy techniques' sensitivity and supports their potential application in environmental biomonitoring. [ABSTRACT FROM AUTHOR]

Petroleum hydrocarbons including polycyclic aromatic hydrocarbons (PAHs) are a pollution issue in the Niger Delta region due to oil industry activities. PAHs were measured in the water column of the Ovia River with concentrations ranging from 0.1 to 1055.6 ng L −1 . Attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy detected alterations in tissues of the African catfish ( Heterobranchus bidorsalis ) from the region showed varying degrees of statistically significant ( P < 0.0001, P < 0.001, P < 0.05) changes to absorption band areas and shifts in centroid positions of peaks. Alteration patterns were similar to those induced by benzo[ a ]pyrene in MCF-7 cells. These findings have potential health implications for resident local communities as H. bidorsalis constitutes a key nutritional source. The study provides supporting evidence for the sensitivity of infrared spectroscopy in environmental studies and supports their potential application in biomonitoring. [ABSTRACT FROM AUTHOR]

Carbon nanotubes (CNTs) are considered promising materials in nanotechnology. We quantified CNT accumulation by the alga Desmodesmus subspicatus . Cells were exposed to radiolabeled CNTs ( 14 C-CNTs; 1 mg/L) to determine uptake and association, as well as elimination and dissociation in clear media. Attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR) was used to detect effects of CNTs on algae. CNT-cell interactions were visualized by electron microscopy and related to alterations in their cell composition. A concentration factor of 5000 L/kg dry weight was calculated. Most of the material agglomerated around the cells, but single tubes were detected in the cytoplasm. Computational analyses of the ATR-FTIR data showed that CNT treated algae differed from controls at all sampling times. CNT exposure changed the biochemical composition of cells. The fact that CNTs are bioavailable for algae and that they influence the cell composition is important with regard to environmental risk assessment of this nanomaterial. [ABSTRACT FROM AUTHOR]

Abstract: Biospectroscopy is an emerging inter-disciplinary field that exploits the application of sensor technologies [e.g., Fourier-transform infrared spectroscopy, Raman spectroscopy] to lend novel insights into biological questions. Methods involved are relatively non-destructive so samples can subsequently be analysed by more conventional approaches, facilitating deeper mechanistic insights. Fingerprint spectra are derived and these consist of wavenumber–absorbance intensities; within a typical biological experiment, a complex dataset is quickly generated. Biological samples range from biofluids to cytology to tissues derived from human or sentinel sources, and analyses can be carried out ex vivo or in situ in living tissue. A reference range of a designated normal state can be derived; anything outside this is potentially atypical and discriminating chemical entities identified. Computational approaches allow one to minimize within-category confounding factors. Because of ease of sample preparation, low-cost and high-throughput capability, biospectroscopy approaches herald a new greener means of environmental health monitoring in urban environments. [Copyright &y& Elsevier]

With increasing production of carbon nanoparticles (CNPs), environmental release of these entities becomes an ever-greater inevitability. However, many questions remain regarding their impact on soil microorganisms. This study examined the effects of long or short multiwalled carbon nanotubes (MWCNTs), C60 fullerene and fullerene soot in Gram-negative bacteria. Attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy was applied to derive signature spectral fingerprints of effects. A concentration-dependent response in spectral alterations was observed for each nanoparticle type. Long or short MWCNTs and fullerene soot gave rise to similar alterations to lipids, Amide II and DNA. The extent of alteration varies with nanoparticle size, with smaller short MWCNTs resulting in greater toxicity than long MWCNTs. Fullerene soot was the least toxic. C60 results in the most distinct and largest overall alterations, notably in extensive protein alteration. This work demonstrates a novel approach for assaying and discriminating the effects of CNPs in target systems. [Copyright &y& Elsevier]

Abstract: In this study, the organization of collagen fibrils within the sclera of the eye was investigated using the 7keV hard X-ray microscope of the Pohang light source and compared to images from electron and atomic force microscopy. From the captured X-ray images, individual collagen fibrils were observed clearly in a spatial resolution much better than 100nm, both in longitudinal sections and in transverse sections. Some of the collagen fibrils showed evidence of axial periodicity. In some regions of the samples, we could see cross-bridge like structures between adjacent collagen fibrils. The X-ray microscope also allowed the observation of keratocytes and the lamella structure of the scleral stroma. The X-ray microscope has some unique advantages in the nano-scale imaging of bio-samples relative to other established imaging techniques. [Copyright &y& Elsevier]

Abstract: A battery of short-term in vitro assays and/or in vivo protocols to evaluate single-agent mutagenicity and/or genotoxicity is available. However, a protocol to assess the effect(s) of complex mixtures in vivo following a positive test finding in vitro remains difficult. Complex interactions may occur in vivo because component pharmacokinetics increases the unpredictability of pharmacodynamic outcomes. The question arises as to whether in vitro mutagenic component(s) of a complex mixture, probably unidentified, reach target organ(s) in vivo at a sufficient concentration. To address the issue of an in vitro positive, standard in vivo chromosome damage assays to test both mixtures and fractions could be conducted but, to assess site-of-contact effects, the alkaline single cell-gel electrophoresis (“comet”) assay or DNA reactivity (e.g., 32P-postlabelling of DNA adducts) might be employed. A newer approach may be the derivation of a “biochemical-cell fingerprint” of potential target sites using infrared microspectroscopy. There is interest in platforms such as gene expression, proteomics, epigenomics or metabolomics as biomarkers of signature genotoxic or non-genotoxic mechanisms. One still needs to address whether a mutagenic and/or genotoxic component reaches a target organ. An approach to track levels of target-organ exposure may be to radio-label components with a short-lived positron-emitting radionuclide. The parent compound retains its physicochemical properties whilst allowing non-invasive in vivo tissue-specific imaging. However, determining target-organ concentration(s) and effect(s) in vivo remains a difficult challenge. [Copyright &y& Elsevier]

Summary: Tamoxifen remains a frontline treatment for hormone-responsive breast cancer despite its use being associated with a 2–7-fold elevated risk of developing endometrial carcinoma. Several groups have investigated whether tamoxifen induces DNA-damaging (genotoxic) versus non-genotoxic mechanisms. Some studies point to the presence of tamoxifen-DNA adducts while others suggest otherwise. In many of these studies, the histological sub-type has not been considered; as type 1 carcinomas are associated with PTEN and KRAS2 mutations whereas type 2 carcinomas exhibit TP53 and ERBB-2 mutations, the absence of this information makes comparisons between such independent investigations difficult. An examination of the sub-types of endometrial carcinoma points to histological and mechanistic distinctions between sporadic and tamoxifen-associated disease; this could suggest differing aetiologies. On this basis, we propose a dual mechanism of action highlighted by the different patterns of endometrial carcinoma sub-types. Tamoxifen may initially be pro-oestrogenic in the endometrium giving rise to elevated type 1 endometrioid carcinoma occurrence whereas after long-term use, there is an increase of type 2 disease or malignant mixed mullerian tumours associated with a hormone-independent mechanism of action. Despite these associated risk factors, and the introduction of new selective oestrogen receptor modulators (SERMs), we suggest that the organ-specific pleiotrophic effects of tamoxifen mean that this effective therapeutic agent for breast cancer will continue to have significant usage. The focus of future research should concentrate on the different aetiologies of tamoxifen-associated endometrial carcinomas while efforts continue to develop future SERMs. [Copyright &y& Elsevier]

Abstract: There is a need to develop risk biomarkers during the remediation of contaminated land. We employed the earthworm, Aporrectodea longa (Ude), to determine whether genotoxicity measures could be applied to this organism''s intestinal tissues. Earthworms were added, for 24h or 7days, to soil samples spiked with benzo[a]pyrene (B[a]P) and/or lindane. After exposure, intestinal tissues (crop/gizzard or intestine) were removed prior to the measurement in disaggregated cells of DNA single-strand breaks (SSBs) by the alkaline comet assay. Damage was quantified by comet tail length (CTL, μm). B[a]P 24-h exposure induced dose-related increases (P&#60;0.0001) in SSBs. Earthworm intestine was significantly (P&#60;0.0001) more susceptible than crop/gizzard to B[a]P and/or lindane. However, both tissues appeared to acquire resistance following 7-day exposure. B[a]P-DNA adducts, measured by 32P-postlabelling, showed a two-adduct-spot pattern. This preliminary investigation suggests that earthworm tissues may be incorporated into genotoxicity assays to facilitate hazard identification within terrestrial ecosystems. [Copyright &y& Elsevier]

Exposure to chemicals such as benzo[ a ]pyrene (B[ a ]P) can generate intracellular toxic mechanisms. Fourier-transform infrared (FTIR) spectroscopy is a novel approach that allows the non-destructive analysis of underlying chemical bond alterations in patho-physiological processes. This study set out to examine whether B[ a ]P-induced whole cell alterations could be distinguished from effects on nuclei of exposed cells. Using attenuated total reflection FTIR (ATR–FTIR) spectroscopy, alterations in nuclei isolated from B[ a ]P-treated MCF-7 cells concentrated either in G 0 /G 1 - or S-phase were observed. B[ a ]P-induced effects in whole-cells included alterations to lipids, DNA and protein spectral regions. Absorbance areas for protein and DNA/RNA regions in B[ a ]P-treated whole cells differed significantly ( P < 0.0001) from vehicle controls and these observations correlated with alterations noted in isolated nuclei. Our findings provide evidence that FTIR spectroscopy has the ability to identify specific chemical-induced alterations. [ABSTRACT FROM AUTHOR]

Highlights: [•] PFOA exposure has been associated with a number of adverse health effects. [•] The molecular mechanisms involved in PFOA hepatotoxicity remain unclear. [•] Differential protein profiles were revealed in PFOA-exposed human hepatic L-02 cells. [•] Induction of apoptosis via p53-dependent pathway is a mechanism of PFOA toxicity. [ABSTRACT FROM AUTHOR]

Abstract: Cancers in hormone-responsive tissues (e.g., breast, ovary, endometrium, prostate) occur at high incidence rates worldwide. However, their genetic basis remains poorly understood. Studies to date suggest that endogenous/exogenous oestrogen and environmental carcinogens may play a role in development and/or progression of hormone-induced cancers via oxidative oestrogen metabolism. Cytochrome P450 1B1 is a key enzyme in its oestrogen metabolism pathway, giving rise to hydroxylation and conjugation. Although CYP1B1 is expressed in many cancers, particularly high levels of expression are observed in oestrogen-mediated disease. CYP1B1 is more readily found in tumour tissue compared to normal. Given the role of CYP1B1 in pro-carcinogen and oestrogen metabolism, polymorphisms in CYP1B1 could result in modifications in its enzyme activity and subsequently lead to hormone-mediated carcinogenesis. CYP1B1 may also be involved in progression of the disease by altering the tissue response to hormones and clinical response to chemotherapy. The exact mechanism behind these events is complex and unclear. Only a few functional single nucleotide polymorphisms of CYP1B1 are known to result in amino acid substitutions and have been extensively investigated. Studies examining the contribution of different CYP1B1 alleles to hormone-mediated cancer risks are inconsistent. The main focus of this review is to appraise the available studies linking the pathogenesis of the hormone-induced cancers to various CYP1B1 polymorphisms. Additionally, we explore the role of a neuronal protein, γ-synuclein, in CYP1B1-mediated pathogenesis. [Copyright &y& Elsevier]

Abstract: Perfluorooctanoic acid (PFOA) is one of the most commonly used perfluorinated compounds. Being a persistent environmental pollutant, it can accumulate in human tissues via various exposure routes. PFOA may interfere in a toxic fashion on the immune system, liver, development, and endocrine systems. In utero human exposure had been associated with cord serum global DNA hypomethylation. In light of this, we investigated possible PFOA-induced DNA methylation alterations in L02 cells in order to shed light into its epigenetic-mediated mechanisms of toxicity in human liver. L02 cells were exposed to 5, 10, 25, 50 or 100mg/L PFOA for 72h. Global DNA methylation levels were determined by LC/ESI-MS, glutathione-S-transferase Pi (GSTP) gene promoter DNA methylation was investigated by methylation-specific polymerase chain reaction (PCR) with bisulfite sequencing, and consequent mRNA expression levels were measured with quantitative real-time reverse transcriptase PCR. A dose-related increase of GSTP promoter methylation at the transcription factor specificity protein 1 (SP1) binding site was observed. However, PFOA did not significantly influence global DNA methylation; nor did it markedly alter the promoter gene methylation of p16 (cyclin-dependent kinase inhibitor 2A), ERα (estrogen receptor α) or PRB (progesterone receptor B). In addition, PFOA significantly elevated mRNA transcript levels of DNMT3A (which mediates de novo DNA methylation), Acox (lipid metabolism) and p16 (cell apoptosis). Considering the role of GSTP in detoxification, aberrant methylation may be pivotal in PFOA-mediated toxicity response via the inhibition of SP1 binding to GSTP promoter. [Copyright &y& Elsevier]

Abstract: The full-length oestrogen receptor (ER) exists in most vertebrates as two separately encoded isoforms. ER splice variants represent truncated or otherwise modified versions of the full-length α or β isoforms of the parent receptor. ERα is found on chromosome 6q and encodes a 595 amino acid protein, while ERβ is found on chromosome 14q and encodes a 530 amino acid protein. These receptors possess differing ligand affinities, are differentially expressed in a tissue-specific fashion and may act antagonistically. Their altered expression has been implicated in the pathophysiology of a diverse range of conditions from cancer progression in hormone-responsive tissues to neurodegenerative disease. Variously co-expressed with full-length ERs, ER splice variants may have a positive or negative influence on transcription either by modifying the effect of the parent receptor or through their own intrinsic activity. To date, the vast majority of studies have used generic primers or antibodies against the full-length receptors and would not distinguish ER-mediated effects associated with various splice variants. Thus the evidence base of the influence of ER splice variants in normal developmental physiology and in the pathogenesis of disease is weak and greater understanding of their role will undoubtedly lead to new therapeutic strategies for disease intervention and treatment. This review aims to compile the current evidence for the presence of ER splice variants in humans, their physiological roles and clinical sequelae. [Copyright &y& Elsevier]

Abstract: One in 10 men in the developed world will present with prostate cancer (CaP), and in an ageing population developing strategies for its chemoprevention or treatment is of significance. For decades, androgen ablation has remained the frontline treatment for CaP that is no longer organ-confined and thus deemed surgically inoperable. Orchidectomy or drug-induced reduction of serum testosterone levels with the consequent removal of growth-promoting effects in the prostate is the driving rationale for this regimen. However, resistance often develops within a few months to years and androgen-insensitive tumours develop. In recent years, there has been an increasing focus on chemoprevention with agents such as finasteride being employed to reduce the risk of developing CaP. Significantly, such chemoprevention strategies are also based on 5α-reductase inhibition thus reducing intraprostatic dihydrotestosterone levels. Although there may be an overall reduction in CaP incidence in cohorts using such chemoprevention, in a subset of users who do develop this pathology there results a more aggressive, higher-grade disease. There have also been suggestions regarding the protective role of androgens against high-grade CaP. This leads to the intriguing notion that 17β-oestradiol (E2) may be an initiating driver of CaP; in fact, in old studies in which CaP was induced in rodents, E2 often accelerated the effect of the carcinogen. Might certain chemoprevention strategies or androgen ablation result in a systemic feedback loop in hormone synthesis or metabolism? If so, elevated serum E2 levels could result in its increased conversion to genotoxic catechol oestrogens in target tissues such as the prostate. Paradoxically, if E2 were to be an initiating factor in CaP, anti-oestrogens might be an overlooked treatment or chemoprevention strategy. [Copyright &y& Elsevier]

• Environmental OCPs exposure in hepatocellular carcinoma is higher than control. • GSTP1 gene promoter DNA methylation but not GSTs polymorphisms associated with HCC. • GSTP1 methylation status plays important roles in OCPs detoxification metabolism. • Interactions between OCPs exposure and GSTP1 genotype as well as epigenetic status involved HCC. Exposure to environmental pollutant organochlorine pesticides (OCPs) and the role of tumour suppressor GSTs gene polymorphisms as well as epigenetic alterations have all been well reported in hepatocarcinogenesis. However, the interplay between environmental risk factors and polymorphic tumour suppressor genes or epigenetic factors in hepatocellular carcinoma (HCC) development remains ambiguous. Herein, we investigated the relationship of three GSTs polymorphisms (GSTT1 deletion, GSTM1 deletion, GSTP1 rs1695) as well as GSTP1 promoter region DNA methylation and HCC risk with a particular focus on the interaction with OCPs exposure among 90 HCC cases and 99 controls in a Chinese population. Serum samples were analysed for OCPs exposure employing gas chromatography coupled with mass selective detector (GC-MS). GSTs polymorphisms and epigenetic alterations were determined using high-resolution melting PCR (HRM PCR) and DNA sequencing. After adjusting for confounders (HBV infection, smoking, alcohol consumption, BMI, age, gender), OCPs exposure and GSTP1 methylation is significantly associated with elevated risk of HCC, while no significance is observed for GSTs polymorphisms. Moreover, the effects of OCPs exposure on HCC risk are more pronounced amongst GSTP1 (Ile/Val + Val/Val) and GSTP1 promoter methylation subjects than those who were GSTP1 (Ile/Ile) and unmethylated subjects. The interactions between OCPs exposure and GSTP1 genotype as well as GSTP1 epigenetic status are statistically significant. The current study demonstrates the importance of gene-environment interactions in the multifactorial development of HCC. [ABSTRACT FROM AUTHOR]

The development and normal function of prostate tissue depends on signalling interactions between stromal and epithelial compartments. Development of a prostate microtissue composed of these two components can help identify substance exposures that could cause adverse effects in humans as part of a non-animal risk assessment. In this study, prostate microtissues composed of human derived stromal (WPMY-1) and epithelial (RWPE-1) cell lines grown in scaffold-free hydrogels were developed and characterized using immunohistochemistry, light microscopy, and qRT-PCR. Within 5 days after seeding, the microtissues self-organized into spheroids consisting of a core of stromal WPMY-1 cells surrounded by epithelial RWPE-1 cells. The RWPE-1 layer is reflective of intermediate prostatic epithelium, expressing both characteristics of the luminal (high expression of PSA) and basal (high expression of cytokeratins 5/6 and 14) epithelial cells. The response of the microtissues to an androgen (dihydrotestosterone, DHT) and an anti-androgen (flutamide) was also investigated. Treatment with DHT, flutamide or a mixture of DHT and flutamide indicated that the morphology and self-organization of the microtissues is androgen dependent. qRT-PCR data showed that a saturating concentration of DHT increased the expression of genes coding for the estrogen receptors (ESR1 and ESR2) and decreased the expression of CYP1B1 without affecting the expression of the androgen receptor. With further development and optimization RWPE-1/WPMY-1 microtissues can play an important role in non-animal risk assessments. • Non-animal risk assessment requires innovative cellular models representative of human biology. • RWPE-1 and WPMY-1 cells form microtissues when grown in scaffold-free hydrogels. • Microtissues represent an early stage of human prostate development. • Morphological and molecular biomarkers are responsive to androgens/anti-androgens. [ABSTRACT FROM AUTHOR]

Highlights • Phthalates' side-chain structures associated with hydrolysis metabolism. • Phthalate metabolites appear to exert different effects at an endocrine level compared to parent compounds. • Hydrolysis metabolism reversed DBP-induced anti-androgenic effects into the androgenic effects. Abstract Although it is well acknowledged that the anti-androgenic phthalate diesters can be readily hydrolysed into their monoester counterparts, their metabolites' toxicology remains obscure. Herein, we tested the hypothesis that hydrolysis of one of the two ester bonds can mediate phthalate diesters' potential endocrine effects in MLTC-1 Leydig cells, in line with their ability to disrupt androgen secretion in humans. Five diesters (DMP, DEP, DBP, DBzP and DEHP) and five monoesters (MMP, MEP, MBP, MBzP and MEHP) phthalates as mixtures or individually were applied to cell lines to investigate differences in phthalates' hydrolysis associated with varying side-chain structures and steroidogenic effects. Short-chain diesters DMP, DEP and DBP are more readily hydrolysed compared to the long-chain DEHP, while aromatic alkyl chain DBzP cannot be metabolized completely in vitro. When the hydrolysis processes are interrupted, the diester phthalates' steroidogenic effects can be influenced via regulating related steroidogenic pathway genes. With 10–100 μM treatment exposures, androgenic effects were observed only with DMP or DEP but not for MMP or MEP; while the phthalate diesters DBP, DBzP or DEHP generally exhibited more complex steroidogenic effects than their corresponding monoester counterparts (i.e. , biphasic androgen and anti-androgen effects for diesters but monotonic androgen effects for monoesters were observed). DBP elicited hydrolysis-related steroidogenic modulation, in which the anti-androgenic effects of diester DBP reversed into the androgenic effects of monoester MBP at 100 μM. Phthalate metabolites appear to exert different effects at an endocrine level compared to parent compounds, and deeper insights into how the hydrolytic process is related to this alternating toxicity would improve our understanding of a risk assessment for these widespread contaminants in male reproduction. [ABSTRACT FROM AUTHOR]

Abstract Herein, vibrational spectroscopy has been applied for qualitative identification of biomolecular alterations that occur in cells and tissues following chemical treatment. Towards this end, we combined attenuated total reflection Fourier-transform infrared (ATR-FTIR) and Raman spectroscopy to assess testicular toxicology after 4-nonylphenol (NP) exposure, an estrogenic endocrine disruptor affecting testicular function in rats and other species. Rats aged 21, 35 or 50 days received NP at intra-peritoneal doses of 0, 25, 50 or 100 mg/kg for 20 consecutive days. Primary Sertoli cells (SCs) were treated with NP at various concentrations (0, 2.5, 5, 10 or 20 μM) for 12 h. Post-exposure, testicular cells, interstitial tissue and SCs were interrogated respectively using spectrochemical techniques coupled with multivariate analysis. Distinct biomolecular segregation between the NP-exposed samples vs. control were observed based on infrared (IR) spectral regions of 3200–2800 cm−1 and 1800-900 cm−1, and the Raman spectral region of 1800–900 cm−1. For in vivo experiments, the main wavenumbers responsible for segregation varied significantly among the three age classes. The main IR and Raman band differences between NP-exposed and control groups were observed for Amide (proteins), lipids and DNA/RNA. An interesting finding was that the peptide aggregation level, Amide Ӏ-to-Amide II ratio, and phosphate-to-carbohydrate ratio were considerably reduced in ex vivo NP-exposed testicular cells or SCs in vitro. This study demonstrates that ATR-FTIR and Raman spectroscopy techniques can be applied towards analysing NP-induced testicular biomolecular alterations. Graphical abstract Image 1 Highlights • The extent of testicular alterations were assessed by ATR-FTIR and Raman spectroscopy. • 4-Nonylphenol (NP) exposure-induced testicular toxicity is associated with biomolecular alterations. • Biomolecular alterations by the age at which NP exposure started were monitored. [ABSTRACT FROM AUTHOR]

Highlights • PXR, SR-B1 and LHR receptor genes were sensitive to PFOA exposure. • PFOA can transport into mitochondria and affect fatty acid mitochondria transport process. • PFOA decreased steroid precursor cholesterol transport and synthesis. • PFOA have biphasic effects on testosterone and progesterone production at varying levels of PFOA exposure. Abstract Perfluorooctanoic acid (PFOA) is a persistent organic pollutant, which may possess endocrine disrupting properties. Herein, we investigated the possible mechanism(s) of toxicity and steroidogenesis in mouse Leydig cells. MLTC-1 (mouse Leydig tumour cells) cells were exposed to 0, 50, 100 or 200 μM PFOA for 48 h to ascertain their effects on the nuclear (membrane) receptor responses, steroidogenesis pathway and related regulated gene expression and steroid hormone secretion profiles. Our results reveal that nuclear receptors PXR , SR-B1 and LHR are sensitive to PFOA exposure. PFOA can accumulate in mitochondria and alter cholesterol precursor (fatty acid) mitochondrial transport process-related gene expression and thus inhibit steroid hormone precursor (cholesterol) production. In particular, PFOA exhibits biphasic effects on testosterone and progesterone production at differing levels of exposure. These findings indicate the potential endocrine-related effects of PFOA on steroid hormone secretion in Leydig cells and point to a novel disruption model. [ABSTRACT FROM AUTHOR]

Robust diagnosis of ovarian cancer is crucial to improve patient outcomes. The lack of a single and accurate diagnostic approach necessitates the advent of novel methods in the field. In the present study, two spectroscopic techniques, Raman and surface-enhanced Raman spectroscopy (SERS) using silver nanoparticles, have been employed to identify signatures linked to cancer in blood. Blood plasma samples were collected from 27 patients with ovarian cancer and 28 with benign gynecological conditions, the majority of which had a prolapse. Early ovarian cancer cases were also included in the cohort ( n  = 17). The derived information was processed to account for differences between cancerous and healthy individuals and a support vector machine (SVM) algorithm was applied for classification. A subgroup analysis using CA-125 levels was also conducted to rule out that the observed segregation was due to CA-125 differences between patients and controls. Both techniques provided satisfactory diagnostic accuracy for the detection of ovarian cancer, with s pontaneous Raman achieving 94% sensitivity and 96% specificity and SERS 87% sensitivity and 89% specificity. For early ovarian cancer, Raman achieved sensitivity and specificity of 93% and 97%, respectively, while SERS had 80% sensitivity and 94% specificity. Five spectral biomarkers were detected by both techniques and could be utilised as a panel of markers indicating carcinogenesis. CA-125 levels did not seem to undermine the high classification accuracies. This minimally invasive test may provide an alternative diagnostic and screening tool for ovarian cancer that is superior to other established blood-based biomarkers. [ABSTRACT FROM AUTHOR]

Amphibians are regarded as sensitive sentinels of environmental pollution due to their permeable skin and complex life cycle, which usually involves reproduction and development in the aquatic environment. Fungicides are widely applied agrochemicals and have been associated with developmental defects in amphibians; thus, it is important to determine chronic effects of environmentally-relevant concentrations of such contaminants in target cells. Infrared (IR) spectroscopy has been employed to signature the biological effects of environmental contaminants through extracting key features in IR spectra with chemometric methods. Herein, the Xenopus laevis (A6) cell line was exposed to low concentrations of carbendazim (a benzimidazole fungicide) or flusilazole (a triazole fungicide) either singly or as a binary mixture. Cells were then examined using attenuated total reflection Fourier-transform IR (ATR-FTIR) spectroscopy coupled with multivariate analysis. Results indicate significant changes in the IR spectra of cells induced by both agents at all concentrations following single exposures, primarily in regions associated with protein and phospholipids. Distinct differences were apparent in the IR spectra of cells exposed to carbendazim and those exposed to flusilazole, suggesting different mechanisms of action. Exposure to binary mixtures of carbendazim and flusilazole also induced significant spectral alterations, again in regions associated with phospholipids and proteins, but also in regions associated with DNA and carbohydrates. Overall these findings demonstrate that IR spectroscopy is a sensitive technique for examining the effects of environmentally-relevant levels of fungicides at the cellular level. The combination of IR spectroscopy with the A6 cell line could serve as a useful model to identify agents that might threaten amphibian health in a rapid and high throughput manner. [ABSTRACT FROM AUTHOR]

This study tested the hypothesis that prepubertal exposure to 4-nonylphenol (NP) affects reproductive function in male rats. Twenty-four rats at five-weeks-old were randomly divided into four groups and treated with NP at varying concentrations (0, 5, 20, and 60 mg/kg/2d) for thirty days by intra-peritoneal injection. 60 mg/kg NP induced spermatogenic degeneration and pronounced deficits in epididymal sperm count, motility and function, whereas potentially stimulatory effects were observed at 5 NP mg/kg. Moreover, 60 mg/kg NP resulted in a significant reduction in fructose, FSH and LH; induced apoptosis related to oxidative stress; inhibited mRNA and protein levels of Bcl-2 and PCNA; as well as the additional up-regulation of p53, Bax, Apaf-1, cytochrome c , cleaved-caspase-3, Fas and FasL expression. Our data suggest potentially hormetic effects of NP on spermatogenic function. High-dose NP impairs testicular development and function by reducing cell proliferation and inducing apoptosis involving oxidative stress-related p53-Bcl-2/Bax and −Fas/FasL pathways. [ABSTRACT FROM AUTHOR]

Epidemiological studies implicate environmental risk factors and epigenetic alterations in the multistage process of hepatocellular carcinoma (HCC) development. However, associations between environmental factors and DNA methylation of tumour suppressor genes (TSGs) in HCC development remain ambiguous. Understanding how possible interactions influence risk may provide insights into the complexity of hepato-carcinogenesis. For this study, blood samples were collected from HCC patients ( n = 90) and healthy volunteers ( n = 99) from Xiamen (China) and data for selected environmental risk factors [e.g., benzo[ a ]pyrene (B[ a ]P), hepatitis B or C virus (HBV or HCV) infection, smoking and alcohol consumption] were recorded; factors identified as significantly higher ( P < 0.05) amongst case subjects compared to controls were identified. In order to assess associations for epigenetic alterations and HCC risk factors, serum DNA methylation of TSGs was quantified using high-resolution melting (HRM) analysis. Our results clearly indicate elevated methylation patterns for detoxification gene [glutathione- S -transferase Pi ( GSTP )] promoter regions in cases compared to control subjects. Additionally, GSTP promoter hypermethylation and B[ a ]P diol epoxide-albumin (BPDE-Alb) were positively correlated with HCC incidence. Our epidemiological and in vitro cell model studies indicated that GSTP promoter DNA methylation regulates this gene's expression. Moreover, GSTP also plays an important role in B[ a ]P detoxification and potential protective role against B[ a ]P-induced liver cell toxicity and hepato-carcinogenesis. [ABSTRACT FROM AUTHOR]