Microplastics are ubiquitous pollutants in the marine environment and a health concern. They are generated directly for commercial purposes or indirectly from the breakdown of larger plastics. ...Examining a toxicological profile for microplastics is a challenge due to their large variety of physico-chemical properties and toxicological behavior. In addition to their concentration, other parameters such as polymer type, size, shape and color are important to consider in their potential toxicity. Microplastics can adsorb pollutants such as polycyclic aromatic hydrocarbons (PAHs) or metals on their surface and are likely to contain plastic additives that add to their toxicity. The observations of microplastics in seafood increased concern for potential human exposure. Since literature considering microplastics in humans is scarce, using a One Environmental Health approach can help better inform about potential human exposures. Marine mammals and sea turtles are long-lived sentinel species regularly used for biomonitoring the health status of the ocean and share trophic chain and habitat with humans. This review considers the available research regarding microplastic and plastic fiber exposures in humans, marine mammals and turtles. Overall, across the literature, the concentration of microplastics, size, color, shape and polymer types found in GI tract and feces from sea turtles, marine mammals and humans are similar, showing that they might be exposed to the same microplastics profile. Additionally, even if ingestion is a major route of exposure due to contaminated food and water, dermal and inhalation studies in humans have provided data showing that these exposures are also health concerns and more effort on these routes of exposures is needed.
In vitro
studies looked at a variety of endpoints showing that microplastics can induce immune response, oxidative stress, cytotoxicity, alter membrane integrity and cause differential expression of genes. However, these studies only considered three polymer types and short-term exposures, whereas, due to physiological relevance, prolonged exposures might be more informative.
Hexavalent chromium Cr(VI) is a known human lung carcinogen with widespread exposure in environmental and occupational settings. Despite well-known cancer risks, the molecular mechanisms of ...Cr(VI)-induced carcinogenesis are not well understood, but a major driver of Cr(VI) carcinogenesis is chromosome instability. Previously, we reported Cr(VI) induced numerical chromosome instability, premature centriole disengagement, centrosome amplification, premature centromere division, and spindle assembly checkpoint bypass. A key regulator of these events is securin, which acts by regulating the cleavage ability of separase. Thus, in this study we investigated securin disruption by Cr(VI) exposure. We exposed human lung cells to a particulate Cr(VI) compound, zinc chromate, for acute (24 h) and prolonged (120 h) time points. We found prolonged Cr(VI) exposure caused marked decrease in securin levels and function. After prolonged exposure at the highest concentration, securin protein levels were decreased to 15.3% of control cells, while securin mRNA quantification was 7.9% relative to control cells. Additionally, loss of securin function led to increased separase activity manifested as enhanced cleavage of separase substrates; separase, kendrin, and SCC1. These data show securin is targeted by prolonged Cr(VI) exposure in human lung cells. Thus, a new mechanistic model for Cr(VI)-induced carcinogenesis emerges with centrosome and centromere disruption as key components of numerical chromosome instability, a key driver in Cr(VI) carcinogenesis.
Marine metal pollution is an emerging concern for human, animal, and ecosystem health. We considered metal pollution in the Sea of Cortez, which is a relatively isolated sea rich in biodiversity. ...Here there are potentially significant anthropogenic inputs of pollution from agriculture and metal mining. We considered the levels of 23 heavy metals and selenium in seven distinct cetacean species found in the area. Our efforts considered two different periods of time: 1999 and 2016/17. We considered the metal levels in relation to (1) all species together across years, (2) differences between suborders Odontoceti and Mysticeti, (3) each species individually across years, and (4) gender differences for each of these comparisons. We further compared metal levels found in sperm whale skin samples collected during these voyages to a previous voyage in 1999, to assess changes in metal levels over a longer timescale. The metals Mg, Fe, Al, and Zn were found at the highest concentrations across all species and all years. For sperm whales, we observed decreased metal levels from 1999 to 2016/2017, except for iron (Fe), nickel (Ni), and chromium (Cr), which either increased or did not change during this time period. These results indicate a recent change in the metal input to the Sea of Cortez, which may indicate a decreased concern for human, animal, and ecosystem health for some metals, but raises concern for the genotoxic metals Cr and Ni. This work was supported by NIEHS grant ES016893 (J.P.W.) and numerous donors to the Wise Laboratory.
•We measured 23 metals and Se in skin of 7 whale species from the Sea of Cortez.•Metal levels appear to be decreasing in these whales over time, except Al, Cr, Fe and Ni remain the same or are increasing.•Our data indicate a similar exposure route across species for Al, Cr, Fe and Ni, likely not dietary.•Al, Cr and Ni are known to be toxic to mammals and may pose a threat to the health of whale populations in the Sea of Cortez.
Besides smoking, lung cancer can be caused by other factors, including heavy metals such as cadmium, nickel, arsenic, beryllium and hexavalent chromium Cr(VI), which is used in multiple settings, ...resulting in widespread environmental and occupational exposures as well as heavy use. The mechanism by which Cr(VI) causes lung cancer is not completely understood. Currently, it is admitted chromosome instability is a key process in the mechanism of Cr(VI)-induced cancer, and previous studies have suggested Cr(VI) impacts the lung tissue in mice by triggering tissue damage and inflammation. However, the mechanism underlying Cr(VI)-induced inflammation and its exact role in lung cancer are unclear. Therefore, this review aimed to systematically examine previous studies assessing Cr(VI)-induced inflammation and to summarize the major inflammatory pathways involved in Cr(VI)-induced inflammation. In cell culture studies, COX2, VEGF, JAK-STAT, leukotriene B4 (LTB4), MAPK, NF-ҡB and Nrf2 signaling pathways were consistently upregulated by Cr(VI), clearly demonstrating that these pathways are involved in Cr(VI)-induced inflammation. In addition, Akt signaling was also shown to contribute to Cr(VI)-induced inflammation, although discrepant findings were reported. Few mechanistic studies were performed in animal models, in which Cr(VI) upregulated oxidative pathways, NF-kB signaling and the MAPK pathway in the lung tissue. Similar to cell culture studies, opposite effects of Cr(VI) on Akt signaling were reported. This work provides insights into the mechanisms by which Cr(VI) induces lung inflammation. However, discrepant findings and other major issues in study design, both in cell and animal models, suggest that further studies are required to unveil the mechanism of Cr(VI)-induced inflammation and its role in lung cancer.
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•Cr(VI) causes lung inflammation as shown in cell culture, animal and human studies.•Cr(VI) regulates many inflammatory pathways, e.g., JAK-STAT, MAPK, NF-ҡB and Akt.•Opposite effects of Cr(VI) on Akt signaling were reported in cell and animal models.
Hexavalent chromium Cr(VI) is considered a major environmental health concern and lung carcinogen. However, the exact mechanism by which Cr(VI) causes lung cancer in humans remains unclear. Since ...several reports have demonstrated a role for inflammation in Cr(VI) toxicity, the present study aimed to apply transcriptomics to examine the global mRNA expression in human lung fibroblasts after acute (24 h) or prolonged (72 and 120 h) exposure to 0.1, 0.2 and 0.3 μg/cm2 zinc chromate, with a particular emphasis on inflammatory pathways. The results showed Cr(VI) affected the expression of multiple genes and these effects varied according to Cr(VI) concentration and exposure time. Bioinformatic analysis of RNA-Seq data based on the Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and MetaCore databases revealed multiple inflammatory pathways were affected by Cr(VI) treatment. qRT-PCR data corroborated RNA-Seq findings. This study showed for the first time that Cr(VI) regulates key inflammatory pathways in human lung fibroblasts, providing novel insights into the mechanisms by which Cr(VI) causes lung cancer.
•Cr(VI) regulates multiple genes in a concentration- and time-dependent manner.•Cr(VI) regulates key inflammatory pathways in human lung fibroblasts.•The regulated inflammatory pathways may be involved in Cr(VI)-induced lung cancer.
Hexavalent chromium Cr(VI) is a global environmental pollutant and human lung carcinogen. However, the mechanisms of Cr(VI) carcinogenesis are not well defined. Cr(VI)-altered gene expression has ...been reported in the literature and is implicated in numerous mechanisms of Cr(VI) carcinogenesis. MicroRNAs (miRNAs) play a key role in controlling gene expression and are associated with carcinogenic mechanisms. To date no studies have evaluated global changes in miRNA expression in human cells after Cr(VI) exposure. We used RNA sequencing to evaluate how a particulate Cr(VI) compound (zinc chromate), the most potent form of Cr(VI), alters global miRNA expression after acute (24 h) or prolonged (72 and 120 h) exposure to 0.1, 0.2 and 0.3 μg/cm2 zinc chromate in an immortalized, non-cancerous human lung cell line (WTHBF-6). Particulate Cr(VI) significantly affected expression of miRNAs at all time points and concentrations tested. We also found the number of significantly downregulated miRNAs increased in a time- and concentration-dependent manner and many miRNAs were upregulated after 24 h exposure at the intermediate concentration tested. Pathway analyses of the differentially expressed miRNAs predicted miRNAs target pathways of Cr(VI) carcinogenesis in a time- and concentration-dependent manner. These data are the first to evaluate global changes in miRNA expression in human lung cells after Cr(VI) exposure and indicate miRNAs may play a key role in pathways of Cr(VI) carcinogenesis.
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•First study evaluating global changes in miRNAs after Cr(VI) exposure in human cells.•Particulate Cr(VI) alters the global expression of miRNAs.•More miRNAs are downregulated following particulate Cr(VI) exposure.•Particulate Cr(VI) affects miRNAs involved in pathways of Cr(VI) carcinogenesis.
Hexavalent chromium Cr(VI) is a global environmental pollutant and human lung carcinogen. However, the mechanisms of Cr(VI) carcinogenesis are not well defined. Cr(VI)-altered gene expression has ...been reported in the literature and is implicated in numerous mechanisms of Cr(VI) carcinogenesis. MicroRNAs (miRNAs) play a key role in controlling gene expression and are associated with carcinogenic mechanisms. To date no studies have evaluated global changes in miRNA expression in human cells after Cr(VI) exposure. We used RNA sequencing to evaluate how a particulate Cr(VI) compound (zinc chromate), the most potent form of Cr(VI), alters global miRNA expression after acute (24 h) or prolonged (72 and 120 h) exposure to 0.1, 0.2 and 0.3 ug/cm
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zinc chromate in an immortalized, non-cancerous human lung cell line (WTHBF-6). Particulate Cr(VI) significantly affected expression of miRNAs at all time points and concentrations tested. We also found the number of significantly downregulated miRNAs increased in a time- and concentration-dependent manner and many miRNAs were upregulated after 24 h exposure at the intermediate concentration tested. Pathway analyses of the differentially expressed miRNAs predicted miRNAs target pathways of Cr(VI) carcinogenesis in a time- and concentration-dependent manner. These data are the first to evaluate global changes in miRNA expression in human lung cells after Cr(VI) exposure and indicate miRNAs may play a key role in pathways of Cr(VI) carcinogenesis.
We are facing a rapidly growing geriatric population (65+) that will live for multiple decades and are challenged with environmental pollution far exceeding that of previous generations. ...Consequently, we currently have a poor understanding of how environmental pollution will impact geriatric health distinctly from younger populations. Few toxicology studies have considered age differences with geriatric individuals. Critically, all top ten most prevalent age-related diseases are linked to metal exposures. Hexavalent chromium Cr(VI) is a metal of major environmental health concern that can induce aging phenotypes and neurotoxicity. However, there are many knowledge gaps for Cr(VI) neurotoxicity, including how Cr(VI) impacts behavior. To address this, we exposed male rats across three ages (3-, 7-, and 18-months old) to Cr(VI) in drinking water (0, 0.05, 0.1 mg/L) for 90 days. These levels reflect the maximum contaminant levels determined by the World Health Organization (WHO) and the U.S. Environmental Protection Agency (US EPA). Here, we report how these Cr(VI) drinking water levels impacted rat behaviors using a battery of behavior tests, including grip strength, open field assay, elevated plus maze, Y-maze, and 3-chamber assay. We observed adult rats were the most affected age group and memory assays (spatial and social) exhibited the most significant effects. Critically, the significant effects were surprising as rats should be particularly resistant to these Cr(VI) drinking water levels due to the adjustments applied in risk assessment from rodent studies to human safety, and because rats endogenously synthesize vitamin C in their livers (vitamin C is a primary reducer of CrVI to CrIII). Our results emphasize the need to broaden the scope of toxicology research to consider multiple life stages and suggest the current regulations for Cr(VI) in drinking water need to be revisited.
•We exposed male rats to Cr(VI) in drinking water at MCLs set by WHO and US EPA.•We assessed behaviors in 5 assays to determine effects across ages (3-, 7-, 18 mo).•Behavior effects were observed as early as 1 week after exposure.•Middle-aged (7-month old) rats were the most impacted age group.•Social and spatial memory were the most impacted behaviors.
Chromosome instability, a hallmark of lung cancer, is a driving mechanism for hexavalent chromium Cr(VI) carcinogenesis in humans. Cr(VI) induces structural and numerical chromosome instability in ...human lung cells by inducing DNA double-strand breaks and inhibiting homologous recombination repair and causing spindle assembly checkpoint (SAC) bypass and centrosome amplification. Great whales are long-lived species with long-term exposures to Cr(VI) and accumulate Cr in their tissue, but exhibit a low incidence of cancer. Data show Cr(VI) induces fewer chromosome aberrations in whale cells after acute Cr(VI) exposure suggesting whale cells can evade Cr(VI)-induced chromosome instability. However, it is unknown if whales can evade Cr(VI)-induced chromosome instability. Thus, we tested the hypothesis that whale cells resist Cr(VI)-induced loss of homologous recombination repair activity and increased SAC bypass and centrosome amplification. We found Cr(VI) induces similar amounts of DNA double-strand breaks after acute (24 h) and prolonged (120 h) exposures in whale lung cells, but does not inhibit homologous recombination repair, SAC bypass, or centrosome amplification, and does not induce chromosome instability. These data indicate whale lung cells resist Cr(VI)-induced chromosome instability, the major driver for Cr(VI) carcinogenesis at a cellular level, consistent with observations that whales are resistant to cancer.
Hexavalent chromium Cr(VI) is a human lung carcinogen with widespread exposure risks. Cr(VI) causes DNA double strand breaks that if unrepaired, progress into chromosomal instability (CIN), a key ...driving outcome in Cr(VI)-induced tumors. The ability of Cr(VI) to cause DNA breaks and inhibit repair is poorly understood in human lung epithelial cells, which are extremely relevant since pathology data show Cr(VI)-induced tumors originate from bronchial epithelial cells. In the present study, we considered immortalized and primary human bronchial epithelial cells. Cells were treated with zinc chromate at concentrations ranging 0.05 to 0.4μg/cm2 for acute (24 h) and prolonged (120 h) exposures. DNA double strand breaks (DSBs) were measured by neutral comet assay and the status of homologous recombination repair, the main pathway to fix Cr(VI)-induced DSBs, was measured by RAD51 foci formation with immunofluorescence, RAD51 localization with confocal microscopy and sister chromatid exchanges. We found acute and prolonged Cr(VI) exposure induced DSBs. Acute exposure induced homologous recombination repair, but prolonged exposure inhibited it resulting in chromosome instability in immortalized and primary human bronchial epithelial cells.
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•Cr(VI) is genotoxic to primary and immortalized human bronchial epithelial cells.•Acute Cr(VI) induces DNA breaks and their repair in human lung epithelial cells.•Prolonged Cr(VI) exposure induces DNA breaks in human bronchial epithelial cells.•Prolonged Cr(VI) exposure inhibits repair in human bronchial epithelial cells.•Particulate Cr(VI) induces chromosome instability in human bronchial epithelial cells.
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