Multiple Adverse Health Effects Research Articles

Cell death induction of dibutyl phthalate (DBP) on primary brain cells from adult zebrafish

The presence of phthalates as plasticizer on pharmaceutical products as well as in aquatic environments requires serious attention. Phthalates are compounds widely used in the manufacturing industry and has been associate with multiple adverse health effects to human. Among the family of phthalates Dibutyl phthalate (DBP) is well used for pharmaceutical products. Limited information however has been generated on the effect of DBP on the brain. The objective of this investigation was to characterize potential neurotoxicity resulting from short term exposure to DBP. Considering the efficacy and sensitivity of the zebrafish model as an early stage- screening tool, and their neurological and biochemical similarities to those of human, this study evaluates the effect of DBP on primary brain cells of the adult zebrafish. This well optimized and implemented methodology can be consider a guide for future studies using primary cells of adult zebrafish given the reduction on reagents, and the number of cells used for treatment. For indirect confirmation of extracted nervous tissue, the Acetylcholinesterase activity (AChEs) assay kit was implemented. In our study primary cells from adult zebrafish brain were exposed to DBP for 24 hours at aerobic environment at concentrations from 3uM to 100μM. The effect on cell viability as well as cell death mechanisms was determined. Results indicate that adult primary brain cells viability is compromised as low as 8uM of DBP. In terms of mechanism, cells undergo apoptosis and autophagy at concentrations of 8μM and 100μM. This study confirms that low concentrations of DBP over a 24-hour period induces apoptosis and autophagy, potentially activating degradation of brain cells and altering biochemical processes of the nervous system. This research presents a novel approach for future molecular studies using brain primary cells as model to screen pharmaceuticals and environmental agents for risk assessment.

US EPA adds 3 PFAS to toxics release reporting

Facilities must start reporting their environmental releases of perfluorooctyl iodide and the potassium and silver(I) salts of perfluorooctanoic acid (PFOA) to the US Environmental Protection Agency. A recent EPA rule requires the reporting to begin for releases in the 2021 calendar year. The chemicals are members of the family of per- and polyfluoroalkyl substances (PFAS), which are environmentally persistent and linked to multiple adverse health effects. The agency added them to the federal Toxics Release Inventory as required by the law that authorized military spending in 2020.

Exploration of the Global Burden of Dementia Attributable to PM2.5: What Do We Know Based on Current Evidence?

Exposure to ambient PM2.5 pollution has been linked to multiple adverse health effects. Additional effects have been identified in the literature and there is a need to understand its potential role in high prevalence diseases. In response to recent indications of PM2.5 as a risk factor for dementia, we examine the evidence by systematically reviewing the epidemiologic literature, in relation to exposure from ambient air pollution, household air pollution, secondhand smoke, and active smoking. We develop preliminary exposure‐response functions, estimate the uncertainty, and discuss sensitivities and model selection. We estimate the likely impact to be 2.1 M (1.4 M, 2.5 M; 5%–95% confidence) global incident dementia cases and 0.6 M (0.4 M, 0.8 M) deaths attributable to ambient PM2.5 pollution in 2015. This implies a combined toll from morbidity and mortality of dementia of 7.3 M (5.0 M, 9.1 M) lost disability‐adjusted life years. China, Japan, India, and the United States had the highest estimated total burden, and the per capita burden was highest in developed countries with large elderly populations. Compared to 2000, most countries in Europe, the Americas, and Southern Africa reduced the burden in 2015, while other regions had a net increase. Based on a recent systematic review of cost of illness studies for dementia, our estimates imply economic costs of US$ 26 billion worldwide in 2015. Based on this estimation, ambient PM2.5 pollution may be responsible for 15% of premature deaths and 7% of DALYs associated with dementia. Our estimates also indicate substantial uncertainty in this relationship, and future epidemiological studies at high exposure levels are especially needed.

Disparities in smokeless tobacco use in Bangladesh, India, and Pakistan: Findings from the Global Adult Tobacco Survey, 2014-2017.

Smokeless tobacco (SLT) use is associated with multiple adverse health effects. It is prominent in Bangladesh, India, and Pakistan, but disparities in use within and across these countries are not well documented or understood. This study assessed the prevalence, patterns, and correlates of SLT use in these three countries. Data came from the Global Adult Tobacco Survey, a household survey of adults aged ≥15 years. Data were collected in 2014 (Pakistan), 2017 (Bangladesh), and India (2016-2017). Current SLT use (nasal or oral use) was defined as reported SLT use daily or less than daily at the time of the survey. Prevalence of both overall and specific SLT types were assessed. Multivariate logistic regression was used to assess correlates of SLT use. Overall, SLT use among adults ≥15 years of age was 20.6% in Bangladesh, 21.4% in India, and 7.7% in Pakistan, corresponding to 22.0 million SLT users in Bangladesh, 199.4 million in India, and 9.6 million in Pakistan. Among current tobacco users overall, the percentage of those who used SLT was 58.4% (CI: 56.0-60.7) in Bangladesh, 74.7% (CI: 73.4-76.0) in India, and 40.3% (CI: 36.2-44.5) in Pakistan. The most commonly used oral SLT product was Zarda (14.5%) in Bangladesh, Khaini (11.2%) in India, and Naswar (5.1%) in Pakistan. Females had greater odds of SLT use than males in Bangladesh, but lower odds of SLT use than males in India and Pakistan. In all three countries, the odds of SLT use was higher among those 25 years and older, lower education, lower wealth index, and greater exposure to SLT marketing. An estimated 231 million adults aged 15 years or older currently use SLT in Bangladesh, India, and Pakistan, comprising 40.3%-74.7% of overall tobacco product use in these countries. Moreover, marked variations in SLT use exist by population groups. Furthermore, exposure to pro-SLT marketing was found to be associated with higher SLT use compared to non-exposed. It is important that tobacco control strategies address all forms of tobacco product use, including SLT.

Copper chloride inhibits brush border membrane enzymes, alters antioxidant and metabolic status and damages DNA in rat intestine: a dose-dependent study.

Copper (Cu) is an extensively used heavy metal and an indispensible micronutrient for living beings. However, Cu is also toxic and exerts multiple adverse health effects when humans are exposed to high levels of this metal. We have examined the effect of single acute oral dose of copper chloride (CuCl2) on parameters of oxidative stress, cellular metabolism, membrane and DNA damage in rat intestine. Adult male Wistar rats were divided into four groups and separately administered a single oral dose of 5, 15, 30 and 40 mg CuCl2/kg body weight. Rats not administered CuCl2 served as the control. Oral administration of CuCl2 led to significant alterations in the activities of metabolic and membrane-bound enzymes; brush border enzymes were inhibited by 45-75% relative to the control set. Inhibition of antioxidant enzymes diminished the metal-reducing and free radical quenching ability of the cells. Oxidative damage caused cellular oxidation of thiols, proteins and lipids. Diphenylamine and comet assays showed that CuCl2 treatment enhanced DNA damage while DNA-protein crosslinking was also increased in the intestinal cells. Examination of stained sections showed that CuCl2 treatment led to marked histological changes in the intestine. All the changes seen were in a CuCl2 dose-dependent manner with more prominent alterations at higher doses of CuCl2. These results clearly show that oral administration of CuCl2 results in oxidative damage to the intestine which can impair its digestive and absorptive functions.

Contribution of tailpipe and non-tailpipe traffic sources to quasi-ultrafine, fine and coarse particulate matter in southern California

ABSTRACT Exposure to traffic-related air pollution (TRAP) in the near-roadway environment is associated with multiple adverse health effects. To characterize the relative contribution of tailpipe and non-tailpipe TRAP sources to particulate matter (PM) in the quasi-ultrafine (PM0.2), fine (PM2.5) and coarse (PM2.5–10) size fractions and identify their spatial determinants in southern California (CA). Month-long integrated PM0.2, PM2.5 and PM2.5–10 samples (n = 461, 265 and 298, respectively) were collected across cool and warm seasons in 8 southern CA communities (2008–9). Concentrations of PM mass, elements, carbons and major ions were obtained. Enrichment ratios (ER) in PM0.2 and PM10 relative to PM2.5 were calculated for each element. The Positive Matrix Factorization model was used to resolve and estimate the relative contribution of TRAP sources to PM in three size fractions. Generalized additive models (GAMs) with bivariate loess smooths were used to understand the geographic variation of TRAP sources and identify their spatial determinants. EC, OC, and B had the highest median ER in PM0.2 relative to PM2.5. Six, seven and five sources (with characteristic species) were resolved in PM0.2, PM2.5 and PM2.5–10, respectively. Combined tailpipe and non-tailpipe traffic sources contributed 66%, 32% and 18% of PM0.2, PM2.5 and PM2.5–10 mass, respectively. Tailpipe traffic emissions (EC, OC, B) were the largest contributor to PM0.2 mass (58%). Distinct gasoline and diesel tailpipe traffic sources were resolved in PM2.5. Others included fuel oil, biomass burning, secondary inorganic aerosol, sea salt, and crustal/soil. CALINE4 dispersion model nitrogen oxides, trucks and intersections were most correlated with TRAP sources. The influence of smaller roadways and intersections became more apparent once Long Beach was excluded. Non-tailpipe emissions constituted ~8%, 11% and 18% of PM0.2, PM2.5 and PM2.5–10, respectively, with important exposure and health implications. Future efforts should consider non-linear relationships amongst predictors when modeling exposures. Implications: Vehicle emissions result in a complex mix of air pollutants with both tailpipe and non-tailpipe components. As mobile source regulations lead to decreased tailpipe emissions, the relative contribution of non-tailpipe traffic emissions to near-roadway exposures is increasing. This study documents the presence of non-tailpipe abrasive vehicular emissions (AVE) from brake and tire wear, catalyst degradation and resuspended road dust in the quasi-ultrafine (PM0.2), fine and coarse particulate matter size fractions, with contributions reaching up to 30% in PM0.2 in some southern California communities. These findings have important exposure and policy implications given the high metal content of AVE and the efficiency of PM0.2 at reaching the alveolar region of the lungs and other organ systems once inhaled. This work also highlights important considerations for building models that can accurately predict tailpipe and non-tailpipe exposures for population health studies.

Recent advances in understanding endocrine disruptors: DDT and related compounds.

Endocrine-disrupting compounds (EDCs) are environmental contaminants that modulate estrogen, androgen, and thyroid hormone receptor signaling and it has been hypothesized that human exposures to EDCs induce multiple adverse health effects. Some of these responses include male and female reproductive tract problems, obesity, and neurological/neurobehavior deficits. Extensive laboratory animal and some human studies support the EDC hypothesis. However, there is a debate among scientists and regulators regarding the adverse human health impacts of EDCs and this review highlights and gives examples of some of the concerns.

Association of Environmental Tobacco Smoke Exposure and Infant Neurodevelopmental Achievements and Effect Modification by Maternal Overweight and Obesity: Results from the Taiwan Birth Cohort Study

Background: Environmental tobacco smoke (ETS) is a common indoor air pollutant associated with multiple adverse health effects, but it remains unclear regarding effect modifiers and susceptible groups for detrimental neurodevelopmental effect of ETS. We examine the associations between ETS exposure and infant neurodevelopmental parameters in a national-wide representative population. Methods: We extracted the information via structured questionnaires upon home interview from Taiwan Birth Cohort Study (TBCS). The associations between ETS exposure and infant neurodevelopmental milestones were evaluated with multivariate conditional logistic regression and the Cox model and with propensity score (PS) weighting and matching based upon preselected covariates. Results: In this study, 15 987 term singletons were included, and 3598 mother-infant pairs were further selected to PS-matched subpopulation. Higher ETS exposure was associated with increased likelihood of delay in caregiver-reported fine motor (adjusted odds ratio (aOR)=1.29, 95% CI=1.07-1.55; adjusted hazard ratio (aHR)=1.06, 95% CI=1.01-1.11 for clapping hands; aOR=1.21, 95% CI=1.03-1.43; aHR=1.05, 95% CI=1.00-1.10 for scribbling), language-related (aOR=1.25, 95% CI=1.03-1.50; aHR=1.08, 95% CI=1.03-1.13 for waving goodbye; aOR=1.22, 95% CI=1.01-1.47; aHR=1.08, 95% CI=1.04-1.14 for calling a parent meaningfully), and it was consistent in PS-weighted, PS-matched, and among non-smoking families. We also detected positive interaction for both maternal overweight and obesity before pregnancy and after delivery upon the association between high ETS exposure and delayed milestone achievement in scribbling. Conclusions: Maternal peripartum ETS exposure was associated with delayed neurodevelopmental milestone achievement at eighteen months among non-smoking families, and effect modification by maternal overweight and obesity status indicated possible intervention targets for pregnant women.

Emerging environmental pollutants hydroxylated polybrominated diphenyl ethers: From analytical methods to toxicology research.

Hydroxylated polybrominated diphenyl ethers (OH-PBDEs) are of particular concern due to their ubiquitous distribution and adverse health effects. Significant progress has been made in the characterization of OH-PBDEs by using mass spectrometry (MS). In this review, we summarize applications of MS-based techniques in detection, environmental and biota distribution, and potential health risk effects, hoping to unfold an overall picture on account of current knowledge of OH-PBDEs. The analytical methodologies are discussed from sample pretreatment to MS analysis. The methods including gas chromatography-MS (GC-MS), liquid chromatography-MS (LC-MS), and ion mobility spectrometry-MS (IMS-MS) are discussed. GC-MS is the most frequently adopted method in the analysis of OH-PBDEs due to its excellent chromatographic resolution, high sensitivity, and strong ability for unknown identification. LC-MS has been widely used for its high sensitivity and capability of direct analysis. As a newly developed technique, IMS-MS provides high specificity, which greatly facilitates the identification of isomers. OH-PBDEs pervasively existed in both abiotic and biotic samples, including humans, animals, and environmental matrices. Multiple adverse health effects have been reported, such as thyroid hormone disruption, estrogen effects, and neurotoxicity. The reported potential pathological mechanisms are also reviewed. Additionally, MS-based metabolomics, lipidomics, and proteomics have been shown as promising tools to unveil the molecular mechanisms of the toxicity of OH-PBDEs. © 2020 John Wiley & Sons Ltd. Mass Spec Rev.

Climate Change and Risk of Completed Suicide

Climate change is increasingly recognized as having multiple adverse mental health effects, many of which are just beginning to be understood. The elevated rates of suicides observed in some communities affected by climate change and rising rates of suicide in the United States as climate change intensifies have suggested the two may be associated. We searched PubMed and PsycInfo using the terms climate change and suicide, and provide here a review of the current literature on climate change and suicide that explores possible associations and methodological issues and challenges in this research.

Epimedium polysaccharides attenuates hematotoxicity by reducing oxidative stress and enhancing immune function in mice model of benzene-induced bone marrow failure

Chronic benzene (BZ) exposure is associated with multiple adverse health effects and leads to progressive bone marrow failure (BMF). BZ-induced BMF is an acquired aplastic anemia characterized by severe anemia, neutropenia and thrombocytopenia, which is likely caused by immunotoxicity and oxidative stress. Previous studies showed that Epimedium polysaccharides (EPS), a natural and major herbal compound derived from Epimedium, has immunomodulatory and antioxidant potential. The purpose of this study was to evaluate the potential efficacy of EPS against BZ-induced BMF. BMF mouse model was established by subcutaneous injection of 2 ml/kg BZ in CD1 mice. Mice received daily oral treatment with 100 mg/kg high-dose EPS and 20 mg/kg low-dose EPS for four weeks. Our data showed that EPS treatment alleviated BZ-associated weight loss and increased the number of whole blood cells in peripheral blood and nucleated cells in bone marrow. Furthermore, EPS treatment decreased apoptotic rate and reactive oxygen species production, S-phase arrest in bone marrow cells. Finally, EPS treatment improved T cell-mediated immune suppression by increasing CD3+, CD4 + T-cell counts, and CD4+/CD8+ ratio. and modulated hematopoietic cytokines including EPO, IL-11, and IL-2 in peripheral blood. Our study suggests that EPS is a potential therapeutic target to attenuate hematotoxicity induced by BZ.

Biomarkers of blood cadmium and incidence of cardiovascular events in non-smokers: results from a population-based proteomics study

BackgroundCadmium is a toxic metal with multiple adverse health effects, including risk of cardiovascular disease (CVD). The mechanistic link between cadmium and CVD is unclear. Our aim was to examine the associations between blood cadmium (B-Cd) and 88 potential protein biomarkers of CVD.MethodsB-Cd and 88 plasma proteins were measured in a community-based prospective cohort, the Malmö Diet and Cancer study. The primary analysis was performed in never smokers (n = 1725). Multiple linear regression was used with adjustments for age and sex, and correction for multiple comparisons using the false discovery rate method. Proteins significantly associated with B-Cd were replicated in long-term former smokers (n = 782). Significant proteins were then studied in relation to incidence of CVD (i.e., coronary events or ischemic stroke) in never smokers.ResultsFifteen proteins were associated with B-Cd in never smokers. Eight of them were replicated in long-term former smokers. Kidney injury molecule-1, fibroblast growth factor-23 (FGF23), tumor necrosis factor receptor-2, matrix metalloproteinase-12, cathepsin L1, urokinase plasminogen activator receptor, C-C motif chemokine-3 (CCL3), and chemokine (C-X3-C motif) ligand-1 were associated with B-Cd both in never smokers and long-term former smokers. Except for CCL3 and FGF23, these proteins were also significantly associated with incidence of CVD.ConclusionsB-Cd in non-smokers was associated with eight potential plasma biomarkers of CVD and kidney injury. The results suggest pathways for the associations between B-Cd and CVD and kidney injury.

Nigella sativaand its Derivatives as Food Toxicity Protectant Agents.

Exposure to food toxins generate multiple adverse health effects. Heavy metals, antibiotics residue, mycotoxins, pesticides and some food additives are examples of the most important food toxins. The common mechanism of toxicity and carcinogenicity effects of food toxins is the generation of oxidative stress that leads to DNA damages. Moreover, based on epidemiologic evidence unhealthy eating habits and food toxicities are associated with cancers occurrence. Therefore, application of bioactive food additives as harmless or safe components in food industry is expensive. Nigella sativa L. is a broadly used herb-drug for various diseases all over the world and has been used as preservative and food additive. Based on various studies N. sativa has shown various pharmacological activities including therapeutic efficacy against different human diseases and antioxidant anti-inflammatory effects against environmental toxins. N. sativa decreases the adverse health effects induced by mentioned food toxins via modulating the action of antioxidant enzymes such as glutathione peroxidase (GPx), glutathione-S-transferase catalase and act as reactive oxygen species (ROS) scavengers in different organs. Besides, N. sativa and thymoquinone (TQ) have protective effects on food products through removal and inhibition of various toxic compounds. Therefore, in the present review we will describe all protective effects of N. sativa and its main constituents, TQ, against food induced toxicities.

The Modulating Role of Sex and Anabolic-Androgenic Steroid Hormones in Cannabinoid Sensitivity

Cannabis is the most commonly used illicit drug worldwide. Although its use is associated with multiple adverse health effects, including the risk of developing addiction, recreational and medical cannabis use is being increasing legalized. In addition, use of synthetic cannabinoid drugs is gaining considerable popularity and is associated with mass poisonings and occasional deaths. Delineating factors involved in cannabis use and addiction therefore becomes increasingly important. Similarly to other drugs of abuse, the prevalence of cannabis use and addiction differs remarkably between males and females, suggesting that sex plays a role in regulating cannabinoid sensitivity. Although it remains unclear how sex may affect the initiation and maintenance of cannabis use in humans, animal studies strongly suggest that endogenous sex hormones modulate cannabinoid sensitivity. In addition, synthetic anabolic-androgenic steroids alter substance use and further support the importance of sex steroids in controlling drug sensitivity. The recent discovery that pregnenolone, the precursor of all steroid hormones, controls cannabinoid receptor activation corroborates the link between steroid hormones and the endocannabinoid system. This article reviews the literature regarding the influence of endogenous and synthetic steroid hormones on the endocannabinoid system and cannabinoid action.

Relating measured moisture of gypsum board to estimated water activity using moisture meters

Dampness and mold in buildings are linked to multiple adverse health effects. The principal factor allowing microbial growth in a material is the water activity (aw), the amount of metabolically available water. To assess the practicality of a portable “aw sensor” that estimates aw by measuring equilibrium relative humidity (ERH) at a surface, we measured the time required, starting at typical room RH, to reach a stable ERH reading on gypsum board at an elevated aw supportive of microbial growth. To estimate aw with commonly used moisture meters, we compared multiple meters (two types: pinless or 2-pin) to each other and to the portable aw sensor, for several gypsum board configurations, at multiple targeted ERH conditions. The aw sensor response was too slow for practical use. Across board configurations (i.e., single or double layers, unpainted or painted, and moisture-resistant), relationships between moisture meter readings and estimated aw differed, as expected, between sorbing and desorbing conditions. Some pinless meters showed inadequate sensitivity to low moisture conditions. Unexpected irregularities in responses were seen, especially on painted board. We provide estimated ranges of moisture meter readings, for each meter and board configuration, corresponding with selected aw values potentially supportive of microbial growth. One or two meters showed most promise for use in estimating critical aw values, although with substantial caveats. The irregularities observed may limit the potential for estimating aw from moisture meter readings in real world applications, even with prior collection of the data needed across different meters, conditions, and building materials.

Neighbour and traffic noise annoyance: a nationwide study of associated mental health and perceived stress.

Noise exposure is a well-known risk factor for multiple adverse health effects. Annoyance is the most prevalent response to environmental noise and may result in negative emotional responses, including poor mental health and high levels of perceived stress. The aim of this study was to investigate the association between neighbour and traffic noise annoyance, and mental health and perceived stress. Data were derived from the Danish Health and Morbidity surveys in 2010 and 2013. The study was based on a random sample of the adult population in Denmark living in multistorey housing (n = 7090). Information on neighbour and traffic noise annoyance during the past 2 weeks, and mental health and perceived stress, using Short Form-12 and Perceived Stress Scale instruments, respectively, was obtained by means of self-administered questionnaires. Multiple logistic regression models were used to examine the associations between noise annoyance and poor mental health, and high perceived stress levels, respectively. Those who reported being very annoyed by neighbour noise had 2.34 [95% confidence interval (CI): 1.83-2.99] times higher odds of having poor mental health and 2.78 (95% CI: 2.25-3.43) times higher odds to experience a high level of perceived stress than individuals not annoyed by noise from neighbours. Similar associations were observed with traffic noise annoyance. The results from this study indicate that there is a strong relationship between noise annoyance and poor mental health and high levels of perceived stress among individuals living in multistorey housing in Denmark. Future studies are needed to determine the direction of causality.

Association between cadmium exposure and diabetes mellitus risk: a prisma-compliant systematic review and meta-analysis.

Cadmium (Cd) is a pollutant with multiple adverse health effects: cancer, renal dysfunction, osteoporosis and fracture, and cardiovascular disease. Several population-based studies found an association between Cd and diabetes mellitus (DM), but this association is inconsistent with other research. We conducted meta-analysis to examine relationship between urinary/blood Cd exposure and DM risk. Pertinent studies were identified by searching PubMed and Embase databases, and combined odds ratio (OR) and corresponding 95% confidence interval (CI) were applied to evaluate said association. Meta-analysis showed that high U-Cd exposure is not correlated with DM risk (OR = 1.19; 95% CI = 0.83–1.71), and high B-Cd exposure is also not associated with increased risk of DM (OR = 1.16; 95% CI = 0.84-1.62) in the general population. Subgroup and sensitivity analysis proved similar results, with little evidence of publication bias. This meta-analysis suggests that high U-Cd/B-Cd exposure may not be risk factor for DM in general populations. However, large prospective studies are needed to confirm this finding.

Temporal Variations in Cigarette Tobacco Bacterial Community Composition and Tobacco-Specific Nitrosamine Content Are Influenced by Brand and Storage Conditions.

Tobacco products, specifically cigarettes, are home to microbial ecosystems that may play an important role in the generation of carcinogenic tobacco-specific nitrosamines (TSNAs), as well as the onset of multiple adverse human health effects associated with the use of these products. Therefore, we conducted time-series experiments with five commercially available brands of cigarettes that were either commercially mentholated, custom-mentholated, user-mentholated, or non-mentholated. To mimic user storage conditions, the cigarettes were incubated for 14 days under three different temperatures and relative humidities (i.e., pocket, refrigerator, and room). Overall, 360 samples were collected over the course of 2 weeks and total DNA was extracted, PCR amplified for the V3V4 hypervariable region of the 16S rRNA gene and sequenced using Illumina MiSeq. A subset of samples (n = 32) was also analyzed via liquid chromatography with tandem mass spectrometry for two TSNAs: N’-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Comparative analyses of the five tobacco brands revealed bacterial communities dominated by Pseudomonas, Pantoea, and Bacillus, with Pseudomonas relatively stable in abundance regardless of storage condition. In addition, core bacterial operational taxonomic units (OTUs) were identified in all samples and included Bacillus pumilus, Rhizobium sp., Sphingomonas sp., unknown Enterobacteriaceae, Pantoea sp., Pseudomonas sp., Pseudomonas oryzihabitans, and P. putida. Additional OTUs were identified that significantly changed in relative abundance between day 0 and day 14, influenced by brand and storage condition. In addition, small but statistically significant increases in NNN levels were observed in user- and commercially mentholated brands between day 0 and day 14 at pocket conditions. These data suggest that manufacturing and user manipulations, such as mentholation and storage conditions, may directly impact the microbiome of cigarette tobacco as well as the levels of carcinogens.

Global Fitness Profiling Identifies Arsenic and Cadmium Tolerance Mechanisms in Fission Yeast.

Heavy metals and metalloids such as cadmium [Cd(II)] and arsenic [As(III)] are widespread environmental toxicants responsible for multiple adverse health effects in humans. However, the molecular mechanisms underlying metal-induced cytotoxicity and carcinogenesis, as well as the detoxification and tolerance pathways, are incompletely understood. Here, we use global fitness profiling by barcode sequencing to quantitatively survey the Schizosaccharomyces pombe haploid deletome for genes that confer tolerance of cadmium or arsenic. We identified 106 genes required for cadmium resistance and 110 genes required for arsenic resistance, with a highly significant overlap of 36 genes. A subset of these 36 genes account for almost all proteins required for incorporating sulfur into the cysteine-rich glutathione and phytochelatin peptides that chelate cadmium and arsenic. A requirement for Mms19 is explained by its role in directing iron–sulfur cluster assembly into sulfite reductase as opposed to promoting DNA repair, as DNA damage response genes were not enriched among those required for cadmium or arsenic tolerance. Ubiquinone, siroheme, and pyridoxal 5′-phosphate biosynthesis were also identified as critical for Cd/As tolerance. Arsenic-specific pathways included prefoldin-mediated assembly of unfolded proteins and protein targeting to the peroxisome, whereas cadmium-specific pathways included plasma membrane and vacuolar transporters, as well as Spt–Ada–Gcn5-acetyltransferase (SAGA) transcriptional coactivator that controls expression of key genes required for cadmium tolerance. Notable differences are apparent with corresponding screens in the budding yeast Saccharomyces cerevisiae, underscoring the utility of analyzing toxic metal defense mechanisms in both organisms.

Genome wide association study identifies two loci associated with cadmium in erythrocytes among never-smokers.

Cadmium is a non-essential toxic metal with multiple adverse health effects. Exposure in the general population occurs by smoking and diet. Cadmium in erythrocytes is a valid biomarker of exposure and body burden of cadmium. We aimed to identify genetic variants related to concentrations of cadmium in erythrocytes. Erythrocyte cadmium was analyzed in 4432 individuals (1728 never smokers) from the Swedish population-based Malmö Diet and Cancer cohort. Genotyping was performed using the Illumina HumanOmniExpressExome Bead chip with genome-wide coverage. Genome wide analyses were performed in the whole sample and in never smokers. No single nucleotide polymorphism (SNP) reached a genome-wide significant association with erythrocyte cadmium in the whole sample. However, in never smokers, 14 variants showed genome-wide significant relationships with erythrocyte cadmium after adjusting for age and sex. Thirteen variants were in linkage disequilibrium on chromosome 8q13.3 in the XKR9 and LACTB2 genes. The lead SNP on 8q13.3 was rs12681420 (minor allele G, minor allele frequency [MAF] = 0.46, β: -0.11, P = 3.48 × 10-11), an intron variant within the XKR9 gene. The other significant locus, rs17574271 (minor allele C, MAF = 0.09, β: 0.17, P = 6.18 × 10-9), was an intron variant within the DLGAP1 gene at chromosome 18p11.31. This genome-wide study of never smokers from the general population identified two independent regions related to erythrocyte cadmium. The strongest locus covers the XKR9 and LACTB2 genes, which both could have related functions in cadmium absorption and metabolism. Replication studies are needed to confirm the findings and mechanisms should be further investigated.