Benzo[a]pyrene at human blood equivalent level induces human lung epithelial cell invasion and migration via aryl hydrocarbon receptor signaling.

Benzo[a]pyrene (B[a]P), a typical carcinogenic polycyclic aromatic hydrocarbon, exists worldwide in vehicle exhaust, cigarette smoke and other polluted environments. Recent studies have demonstrated a strong association between B[a]P and lung cancer. However, whether B[a]P at human blood equivalent level can promote epithelial-mesenchymal transition (EMT), a crucial molecular event during cell malignant transformation, remains unclear. Besides, whether B[a]P facilitates this progress via aryl hydrocarbon receptor (AhR) signaling pathway also lacks scientific evidence. In our study, the transwell assay showed that 5 µg/L of B[a]P promoted BEAS-2B cell invasion and migration. In addition, the mRNA and protein expression levels of AhR and its target genes involved in B[a]P metabolism, such as AhR nuclear translocator, heat shock protein 90 and CYP1A1, were significantly increased by B[a]P exposure. Moreover, the mRNA expression levels of downstream regulatory factors related to both AhR signaling pathway and EMT, such as NRF2, K-RAS and hypoxia-inducible factor 1-alpha, were significantly increased. Furthermore, the expression level of the epithelial marker E-cadherin was significantly downregulated, while the mRNA expression of mesenchymal phenotype markers, N-cadherin, fibronectin and vimentin, were significantly upregulated. Notably, the above changes induced by B[a]P were significantly attenuated or even stopped by resveratrol (RSV), a natural phenol, also an AhR inhibitor, when the AhR signaling pathway was inhibited by RSV, demonstrating the regulatory role of AhR signaling pathway in B[a]P-induced EMT. In conclusion, B[a]P at the human blood equivalent level induces BEAS-2B cell invasion and migration through the AhR signaling pathway.

Flavored Versus Nonflavored Waterpipe Tobacco: A Comparison of Toxicant Exposure, Puff Topography, Subjective Experiences, and Harm Perceptions.

INTRODUCTION: Flavored waterpipe (WP) tobacco is the main type of tobacco used by young WP smokers, and a major factor attracting youth to smoke. However, evidence regarding the effect of limiting flavor on WP smokers' experience continues to be lacking. This study aims at evaluating the effect of flavor restriction on WP smokers' toxicant exposure, smoking topography, subjective experiences and harm perception. METHODS: Thirty-two WP smokers completed two, 45-minute ad libitum smoking sessions (preferred flavor vs non-flavored tobacco) in a crossover design pilot study. Plasma nicotine concentration and exhaled carbon monoxide (eCO) were measured before and after each smoking session. Puff topography was recorded throughout the smoking session. Participants completed survey questionnaires assessing subjective smoking experiences and harm perception. RESULTS: Significant differences were observed in plasma nicotine concentration between the two WP tobacco conditions, with a higher increase in plasma nicotine concentration following the flavored tobacco session. There were no significant differences between the two WP tobacco conditions for eCO and smoking topography measures. Compared with the non-flavored WP tobacco, we documented enhanced subjective smoking measures of satisfaction, calmness, taste, puff liking and enjoyment following the preferred flavored WP tobacco session. Cigarette harm perception was significantly higher among participants after smoking their preferred flavor compared with non-flavored WP tobacco. CONCLUSIONS: Limiting tobacco flavor has a substantial effect on WP smokers' nicotine exposure, subjective experience and harm perception. Therefore, eliminating or restricting WP flavors could be an essential element of comprehensive tobacco control policies to reduce the appeal of WP tobacco products for youth. IMPLICATIONS: This study highlights the important role of flavor in shaping WP smokers' experiences and exposures and the potential impact that regulating flavored WP tobacco may have on curbing WP use among youth in the US. Such regulations may reduce the appeal and the interest in WP smoking initiation and continued use.

Biomarkers of Tobacco Exposure Decrease After Smokers Switch to an E-Cigarette or Nicotine Gum.

INTRODUCTION: The aerosol composition of electronic cigarettes (ECs) suggests that exposure to toxicants during use is greatly reduced compared to exposure from combustible cigarettes (CCs). METHODS: This randomized, parallel-group, clinical study enrolled smokers to switch to Vuse Solo (VS) Digital Vapor Cigarettes (Original or Menthol) or Nicorette 4 mg nicotine gum (NG) in a controlled setting. Subjects who smoked CCs ad libitum for 2 days during a baseline period were then randomized to ad libitum use of either VS or NG for 5 days. Biomarkers of 23 toxicants were measured in 24-hour urine samples and blood collected at baseline and following product switch. RESULTS: A total of 153 subjects completed the study. Total nicotine equivalents decreased in all groups, but higher levels were observed in the VS groups compared to the NG groups, with decreases of 38% and 60%-67%, respectively. All other biomarkers were significantly decreased in subjects switched to VS, and the magnitude of biomarker decreases was similar to subjects switched to NG. Decreases ranged from 30% to greater than 85% for constituents such as benzene and acrylonitrile. CONCLUSIONS: These results indicate that exposure to toxicants when using VS is significantly reduced compared to CC smoking, and these reductions are similar to those observed with use of NG. Although statistically significantly decreased, nicotine exposure is maintained closer to CC smoking with VS use compared to NG use. This research suggests that use of VS exposes consumers to fewer and lower levels of smoke toxicants than CCs while still providing nicotine to the consumer. IMPLICATIONS: This is the first study to report changes in nicotine delivery and biomarkers of tobacco exposure following a short-term product switch from CCs to either an EC or NG in a controlled environment. The study shows that nicotine exposure decreased in both groups but was maintained closer to CC smoking with the EC groups. Biomarkers of tobacco combustion decreased to similar levels in both EC and gum groups.

The Argentinian mother-and-child contaminant study: a cross-sectional study among delivering women in the cities of Ushuaia and Salta.

Several ongoing international multidisciplinary projects have examined linkages between environmental chemicals and health. In contrast to Arctic regions, information for the Southern Hemisphere is scarce. Because of the inherent practice of pesticide utilisation and mismanagement, food security is potentially threatened. The most vulnerable period in human life occurs during pregnancy and early childhood, thus a focus on the body burdens of PTS in pregnant or delivering women is warranted. The current study was designed to investigate health risks related to exposure to PTS and food security in two regions of Argentina (Ushuaia and Salta). Our aims were to quantify concentrations of organic and inorganic toxins in serum or whole blood of delivering women and to collect pertinent dietary and medical information. The overall study design, the basic demographic features and essential clinical chemistry findings are described in the current paper. The socioeconomic differences between the two study areas were evident. On average, the women in Ushuaia were 4 years older than those in Salta (28.8 vs. 24.7 years). Respectively, the proportion of current smokers was 4.5 vs. 9.6%; and Salta had a higher birth rate, with 15.6% being para four or more. Saltanean women reported longer breastfeeding periods. Caesarean sections were more frequent in Ushuaia, with 43% of Caesarean deliveries compared with only 6% in Salta. Employment was high in both communities. Recognised environmental pollution sources in the vicinity of participant dwellings were widespread in Salta (56.1%) compared to Ushuaia (9%). The use of pesticides for insect control in homes was most common in Salta (80%). There is an urgent need for a comprehensive assessment of exposures in areas of the Southern Hemisphere. Our data set and the planned publications of observed concentrations of inorganic and organic environmental contaminants in both mothers and their newborns will contribute to this objective.

Contamination index. A novel parameter for metal and pesticide analyses in maternal blood and umbilical cord

ABSTRACT PURPOSE: To evaluate the contamination index of metals and pesticides in pregnant women, and to relate this to perinatal outcomes. METHODS: Descriptive, retrospective, exploratory study, developed from existing secondary data analyses at Level III maternity center. A total of 40 mothers with their newborns (NB), living in a rural area in Botucatu- Brazil and surrounding region. Blood samples from mothers and newborn were collected to determine the total contamination index for metals and pesticides. The concentrations of each metal and each pesticide were determined in blood samples of mothers and their newborns by Rudge's results. After obtaining these concentrations, the total contamination index in mother and NB was calculated, along with its correlation with clinical parameters of NB. RESULTS: There was no correlation (p> 0.05) between maternal contamination index with NB clinical parameters, and NB contamination index versus NB clinical parameters. CONCLUSION: The maternal contamination index of metals and pesticides was not related to perinatal outcomes, but it could be used as baseline parameter in future toxicological studies, regarding to long-term toxic characteristics as persistent organic pollutants, its long half-lives, bioacumulative, and expected to impose serious health effects on humans.

Preconcentration and determination of lead and cadmium levels in blood samples of adolescent workers consuming smokeless tobacco products in Pakistan.

The present study was aimed to evaluate the cadmium (Cd) and lead (Pb) levels in the blood samples of adolescent boys, chewing different smokeless tobacco (SLT) products in Pakistan. For comparative purpose, boys of the same age group (12-15 years), not consumed any SLT products were selected as referents. To determine trace levels of Cd and Pb in blood samples, a preconcentration method, vortex-assisted liquid-liquid microextraction (VLLME) has been developed, prior to analysis by flame atomic absorption spectrometry. The hydrophobic chelates of Cd and Pb with ammonium pyrrolidinedithiocarbamate were extracted into the fine droplets of ionic liquid (IL) 1-butyl-3-methylimidazolium hexafluorophosphate, while nonionic surfactant, Triton X-114 was used as a dispersing medium. The main factors affecting the recoveries of Cd and Pb, such as concentration of APDC, centrifugation time, volume of IL and TX-114, were investigated in detail. It was also observed that adolescent boys who consumed different SLT products have 2- to 3-fold higher levels of Cd and Pb in their blood samples as compared to referent boys (p < 0.001).

Human bio-monitoring study--toxic elements in blood of women.

The article describes bio-monitoring study concerning recent and long-term exposure of Czech women to toxic metals. Blood cadmium, mercury and lead levels were measured in groups of women with various life styles, etc., to have comparable results in the course of a long study period; a strong emphasis was laid on the quality control of the whole process during the study. Higher cadmium level was found in smokers compared to non-smokers, lower mercury level was found in the group of women who never eat fish. A slight increase of blood lead level with age was observed. No significant differences were found between localities in a given period. Our results do not differ from those gained in other European countries.

The association between active/passive smoking and toxic metals among pregnant women in Greece.

Exposure to toxic metals during pregnancy may have detrimental effects on foetal development. We assessed the role of sociodemographic characteristics and active and passive smoking on blood concentrations of metals (As, Cd, Pb, Hg, Sb, U, Mn and Mo). Venous blood drawn from 50 pregnant women, randomly selected from the mother-child birth cohort 'Rhea'. Extensive questionnaire data on active and passive smoking were collected. Urinary cotinine was measured to validate self-reported exposure and non-smoking status. Smokers had higher concentrations of Cd (1.0 µg/L) as compared with non-smokers (0.29 µg/L, P < 0.001) and a tendency for higher As and Hg. Among non-smokers, blood As and Hg concentrations were also associated with exposure to passive smoking in public venues and the family home and to overall greater secondhand smoke (SHS) exposure (As: 0.97µg/L among heavy-exposed compared with 0.20 µg/L among the low-exposed, P < 0.05; Hg: 2.1 µg/L vs. 0.9 µg/L respectively, P < 0.05). Controlling for fish and seafood intake altered the statistical significance but not the direction of the above associations. Smoking was associated with higher Cd concentrations in pregnant women, although the association between passive smoking and elevated As and Hg concentrations was indicative, however inconclusive.

Effect of gestational smoke exposure on atopic dermatitis in the offspring.

The adverse impact of smoking on respiratory diseases and birth outcomes in children is well-known. However, the influence of smoke exposure including environmental tobacco smoke (ETS) and maternal smoking during pregnancy on atopic dermatitis (AD) is not clear. The purpose of this study was to evaluate the effect of gestational smoke exposure on the development of AD in the offspring on the basis of the maternal and cord blood cotinine. We recruited 261 mother and newborn pairs in 2004. Cord blood and information on perinatal factors of children were gathered at birth. At 2 yr of age, information about development of AD and environmental exposures were collected. We compared AD with non-AD children for the concentration of cotinine in cord and maternal blood measured by high performance liquid chromatography-mass spectrometry. Multiple logistic regressions were performed to estimate the relationship of cotinine levels and AD. About 150 mother and child pairs completed the follow-up study and specimen collection with 38 (25.3%) children developing AD. Two (1.3%) out of 150 mothers smoked during pregnancy, while 38 (25.3%) mothers reported having ETS exposure. Cotinine levels in cord blood and maternal blood were highly correlated (r = 0.71, p < 0.001). The risk of AD was found to increase with maternal and cord blood cotinine levels in a dose-response manner (p for trend = 0.01). Children exposed to high levels (>75th percentile) had a significantly increased risk of AD. Smoke exposure during pregnancy might increase the risk of AD in children. Avoidance of prenatal smoke exposure may be warranted for early prevention.

Gender differences in the disposition and toxicity of metals.

There is increasing evidence that health effects of toxic metals differ in prevalence or are manifested differently in men and women. However, the database is small. The present work aims at evaluating gender differences in the health effects of cadmium, nickel, lead, mercury and arsenic. There is a markedly higher prevalence of nickel-induced allergy and hand eczema in women compared to men, mainly due to differences in exposure. Cadmium retention is generally higher in women than in men, and the severe cadmium-induced Itai-itai disease was mainly a woman's disease. Gender differences in susceptibility at lower exposure are uncertain, but recent data indicate that cadmium has estrogenic effects and affect female offspring. Men generally have higher blood lead levels than women. Lead accumulates in bone and increased endogenous lead exposure has been demonstrated during periods of increased bone turnover, particularly in women in pregnancy and menopause. Lead and mercury, in the form of mercury vapor and methylmercury, are easily transferred from the pregnant women to the fetus. Recent data indicate that boys are more susceptible to neurotoxic effects of lead and methylmercury following exposure early in life, while experimental data suggest that females are more susceptible to immunotoxic effects of lead. Certain gender differences in the biotransformation of arsenic by methylation have been reported, and men seem to be more affected by arsenic-related skin effect than women. Experimental studies indicate major gender differences in arsenic-induced cancer. Obviously, research on gender-related differences in health effects caused by metals needs considerable more focus in the future.

Blood lead and erythrocyte protoporphyrin levels in association with smoking and personal hygienic behaviour among lead exposed workers.

AIMS: To investigate the effects of smoking and personal hygienic behaviour on blood lead (BPb) and free erythrocyte protoporphyrin levels (FEP) in lead exposed workers. METHODS: Subjects were 105 lead exposed male workers in a battery recycling plant during the years 2000-03. BPb and FEP were measured as part of the ongoing occupational surveillance. Each worker completed a questionnaire for assessment of smoking and four measures of personal hygienic behaviour (glove and mask use, hand and face washing before meals during working hours). RESULTS: Statistically significant decreases in mean BPb and FEP occurred during the three years. The proportion of BPb reduction in the non-smoking workers was significantly higher (mean 24.3%) than in the smoking workers (15.3%). When the workers were classified into three groups (excellent, good, and poor) based on the four personal hygienic behavioural indicators, the greatest decreases of BPb and FEP were observed in the non-smoking workers of the excellent group. CONCLUSIONS: The consistent use of protection devices and cleanliness at work appeared to contribute to the lowering of BPb and FEP. Cessation of smoking in the workplace was also of importance.

A simple automated procedure for the detection and identification of peaks in gas chromatography--continuous scan mass spectrometry. Application to systematic toxicological analysis of drugs in whole human blood.

Gas chromatography-mass spectrometry (GC-MS), which combines the separation power of GC with the power of MS for the identification of unknown compounds, possesses high potential in systematic toxicological analysis (STA). Different factors, however, do not allow this potential to be fully exploited. Between them, the low selectivity of the mass spectrometer operating in continuous scan plays a critical role, in many cases precluding the possibility of selecting mass spectra in the total ion chromatogram (TIC) sufficiently clean for a positive identification by library search, even when using reverse search algorithms. Moreover, the large amount of information contained in GC-MS data file that results from the analysis of a biological extract makes the efforts of manual search almost useless and requires the availability of reliable methods for the automated detection and identification of peaks in a TIC. In this paper, a simple procedure that improves the performance of a bench-top GC-MS system in the purification of mass spectra of coeluting compounds and that can be easily combined with the automated processing of a GC-MS data file is described. It is based on the subtraction of the intensities of successive pairs of scans in the TIC, on the detection of positive and negative peaks in the transformed chromatograms, and on the search of the corresponding background-subtracted electron ionization mass spectra against reference libraries. In order to evaluate the proposed procedure, GC-MS data files obtained for the analysis of extracts of blank whole blood spiked with more than 100 drugs, poisons, and their metabolites at a concentration of 0.5 mg/L were used. Compared with the search of the raw TICs, the proposed procedure increased the number of identified substances and, in many cases, obtained higher match quality values for identification.

Factores embriotóxicos tempranos como posible mecanismo de infertilidad en pacientes con aborto habitual y esterilidad sin causa aparente / Embryologic toxic factors as infertility cause in patients habitual abortions with sterility without apparent cause

El objetivo del presente estudio es identificar la presencia de factores embriotóxicos tempranos como causa de infertilidad. Se estudia 15 sueros de pacientes divididos en dos grupos: de abortos habituales y con esterilidad sin causa aparente. Se realizó cultivo de embriones preimplantacionales de ratón que permite identificar en el suero de mujeres agentes embriotóxicos y mutagénicos incompatibles con el desarrollo embrionario.