A preliminary study of Argiope argentata as indicators of southern California metal contamination

This study describes a novel test for 16 metals using Argiope argentata as indicators of environmental pollution. Our results suggest that A. argentata from a relatively isolated California island suffer a more diverse metal burden than those from the California mainland. Metal burdens of Cd, Cs, Ni, Sr, Tl, and U were greater in Santa Catalina specimens. Only the metal burdens of As and V were greater in the mainland Encinitas specimens. The metal burdens of Be, Bi, Co, Cr, Ga, In, Li, and Pb were not different between the sites. Soil samples taken later from the same sampling locations confirm higher concentrations of Cd, Ni and Sr on Santa Catalina, while cactus plants from the sites had a different pattern of metal accumulation. The effect of metal burden on spider body weight was examined, and Santa Catalina A. argentata had significantly increased mass compared to Encinitas spiders. This indicates that, despite a more diverse burden of metals, A. argentata spiders from Santa Catalina may have a higher fitness than those from Encinitas

Metabolism and Lung Toxicity of Inhaled Naphthalene: Effects of Postnatal Age and Sex.

Human exposure to naphthalene (NA), an acute lung toxicant and possible human carcinogen, is primarily through inhalation. Acute lung toxicity and carcinogenesis are thought to be related because the target sites for both are similar. To understand susceptibility of the developing lung to cytotoxicity of inhaled NA, we exposed neonatal (7 days), juvenile (3 weeks), and adult mice to 5 or 10 ppm NA vapor for 4 h. We measured vacuolated airway epithelium morphometrically, quantified NA and NA-glutathione levels in plasma and lung, and quantified gene expression in microdissected airways. NA inhalation caused airway epithelial cytotoxicity at all ages, in both sexes. Contrary to a previous study that showed the greatest airway epithelial cytotoxicity in neonatal mice following intraperitoneal NA injection, we observed the most extensive airway epithelial toxicity in older, juvenile, animals exposed to NA by inhalation. Juvenile female animals were the most susceptible. Furthermore, NA inhalation in juvenile animals resulted in damage to conducting airway Club cells that was greater in proximal versus distal airways. We also found NA tissue burden and metabolism differed by age. Gene expression pathway analysis was consistent with the premise that female juvenile mice are more predisposed to damage; DNA damage and cancer pathways were upregulated. Our data demonstrate special susceptibility of young, juvenile mice to NA inhalation-induced cytotoxicity, highlight the importance of route of exposure and airway location in toxicity of chemicals in the developing lung, and provide metabolic and molecular insights for further identification of mechanisms underlying age and sex differences in NA toxicity

Naphthalene DNA adduct formation and tolerance in the lung

Naphthalene (NA) is a respiratory toxicant and possible human carcinogen. NA is a ubiquitous combustion product and significant component of jet fuel. The National Toxicology Program found that NA forms tumors in two species, in rats (nose) and mice (lung). However, it has been argued that NA does not pose a cancer risk to humans because NA is bioactivated by cytochrome P450 monooxygenase enzymes that have very high efficiency in the lung tissue of rodents but low efficiency in the lung tissue of humans. It is thought that NA carcinogenesis in rodents is related to repeated cycles of lung epithelial injury and repair, an indirect mechanism. Repeated in vivo exposure to NA leads to development of tolerance, with the emergence of cells more resistant to NA insult. We tested the hypothesis that tolerance involves reduced susceptibility to the formation of NA-DNA adducts. NA-DNA adduct formation in tolerant mice was examined in individual, metabolically-active mouse airways exposed ex vivo to 250 μΜ 14C-NA. Ex vivo dosing was used since it had been done previously and the act of creating a radioactive aerosol of a potential carcinogen posed too many safety and regulatory obstacles. Following extensive rinsing to remove unbound 14C-NA, DNA was extracted and 14C-NA-DNA adducts were quantified by AMS. The tolerant mice appeared to have slightly lower NA-DNA adduct levels than non-tolerant controls, but intra-group variations were large and the difference was statistically insignificant. It appears the tolerance may be more related to other mechanisms, such as NA-protein interactions in the airway, than DNA-adduct formation

Comparison of acute respiratory epithelial toxicity for 4-Methylimidazole and naphthalene administered by oral gavage in B6C3F1 mice

4-Methylimidazole (4MEI) is a contaminant in food and consumer products. Pulmonary toxicity and carcinogenicity following chronic dietary exposures to 4MEI is a regulatory concern based on previous rodent studies. This study examined acute pulmonary toxicity in B6C3F1 mice from 6 h to 5 days after oral gavage with a single dose of 150 mg/kg 4MEI, a double dose delivered 6 h apart, or vehicle controls. Oral gavage of 150 mg/kg naphthalene, a prototypical Club cell toxicant, was used as a positive control. Intrapulmonary conducting airway cytotoxicity was assessed in fixed-pressure inflated lungs using qualitative histopathology scoring, quantitative morphometric measurement of vacuolated and exfoliating epithelial cells, and immunohistochemistry. 4MEI treatment did not change markers of cytotoxicity including the mass of vacuolated epithelium, the thickness of the epithelium, or the distributions of epithelial proteins: secretoglobin 1A1, proliferating cell nuclear antigen, calcitonin gene-related peptide, and myeloperoxidase. 4MEI and vehicle controls caused slight cytotoxicity with rare vacuolization of the epithelium relative to the severe bronchiolar epithelial cell toxicity found in the naphthalene exposed mice at terminal bronchioles, intrapulmonary airways, or airway bifurcations. In summary, 4MEI caused minimal airway epithelial toxicity without characteristic Club Cell toxicity when compared to naphthalene, a canonical Club Cell toxicant

Naphthalene genotoxicity: DNA adducts in primate and mouse airway explants

Naphthalene (NA) is a ubiquitous environmental pollutant and possible human carcinogen that forms tumors in rodents with tissue/regional and species selectivity. This study seeks to determine whether NA is able to directly adduct DNA in an ex vivo culture system. Metabolically active lung tissue was isolated and incubated in explant culture with carbon-14 labeled NA (0, 25, 250 μM) or 1,2-naphthoquinone (NQ), followed by AMS analyses of metabolite binding to DNA. Despite relatively low metabolic bioactivation in the primate airway, dose-dependent NA-DNA adduct formation was detected. More airway adducts were detected in female mice (4.7-fold) and primates (2.1-fold) than in males of the same species. Few adducts were detected in rat airway or nasal epithelium. NQ, which is a metabolic product of NA, proved to be even more potent, with levels of adduct formation 70-80-fold higher than seen when tissues were incubated with the parent compound NA. This is the first study to demonstrate NA-DNA adduct formation at a site of carcinogenesis, the mouse lung. Adducts were also detected in non-human primate lung and with a NQ metabolite of NA. Taken together, this suggests that NA may contribute to in vivo carcinogenesis through a genotoxic mechanism

Novel multi-functional europium-doped gadolinium oxide nanoparticle aerosols facilitate the study of deposition in the developing rat lung.

Ambient ultrafine particulate matter (UPM), less than 100 nm in size, has been linked to the development and exacerbation of pulmonary diseases. Age differences in susceptibility to UPM may be due to a difference in delivered dose as well as age-dependent differences in lung biology and clearance. In this study, we developed and characterized aerosol exposures to novel metal oxide nanoparticles containing lanthanides to study particle deposition in the developing postnatal rat lung. Neonatal, juvenile and adult rats (1, 3 and 12 weeks old) were nose only exposed to 380 μg m(-3) of ∼30 nm europium doped gadolinium oxide nanoparticles (Gd2O3:Eu(3+)) for 1 h. The deposited dose in the nose, extrapulmonary airways and lungs was determined using inductively-coupled plasma mass spectroscopy. The dose of deposited particles was significantly greater in the juvenile rats at 2.22 ng per g body weight compared to 1.47 ng per g and 0.097 ng per g for the adult and neonate rats, respectively. Toxicity was investigated in bronchoalveolar lavage fluid (BALF) by quantifying recovered cell types, and measuring lactate dehydrogenase activity and total protein. The toxicity data suggests that the lanthanide particles were not acutely toxic or inflammatory with no increase in neutrophils or lactate dehydrogenase activity at any age. Juvenile and adult rats had the same mass of deposited NPs per gram of lung tissue, while neonatal rats had significantly less NPs deposited per gram of lung tissue. The current study demonstrates the utility of novel lanthanide-based nanoparticles to study inhaled particle deposition in vivo and has important implications for nanoparticles delivery to the developing lung either as therapies or as a portion of particulate matter air pollution

Additional file 1 of CITEViz: interactively classify cell populations in CITE-Seq via a flow cytometry-like gating workflow using R-Shiny

Additional file 1. Back-gate schemes for B-cells and platelets, and an example gate using scRNA-Seq data

Novel multi-functional europium-doped gadolinium oxide nanoparticle aerosols facilitate the study of deposition in the developing rat lung

Ambient ultrafine particulate matter (UPM), less than 100 nm in size, has been linked to the development and exacerbation of pulmonary diseases. Age differences in susceptibility to UPM may be due to a difference in delivered dose as well as age-dependent differences in lung biology and clearance. In this study, we developed and characterized aerosol exposures to novel metal oxide nanoparticles containing lanthanides to study particle deposition in the developing postnatal rat lung. Neonatal, juvenile and adult rats (1, 3 and 12 weeks old) were nose only exposed to 380 μg/m(3) of ~30 nm europium doped gadolinium oxide nanoparticles (Gd(2)O(3):Eu(3+)) for 1 h. The deposited dose in the nose, extrapulmonary airways and lungs was determined using inductively-coupled plasma mass spectroscopy. The dose of deposited particles was significantly greater in the juvenile rats at 2.22 ng/g body weight compared to 1.47 ng/g and 0.097 ng/g for the adult and neonate rats, respectively. Toxicity was investigated in bronchoalveolar lavage fluid (BALF) by quantifying recovered cell types, and measuring lactate dehydrogenase activity and total protein. The toxicity data suggests that the lanthanide particles were not acutely toxic or inflammatory with no increase in neutrophils or lactate dehydrogenase activity at any age. Juvenile and adult rats had the same mass of deposited NPs per gram of lung tissue, while neonatal rats had significantly less NPs deposited per gram of lung tissue. The current study demonstrates the utility of novel lanthanide-based nanoparticles to study inhaled particle deposition in vivo and has important implications for nanoparticles delivery to the developing lung either as therapies or as a portion of particulate matter air pollution