Phenomic profiling to reveal tolerance mechanisms and regulation of ascorbate-glutathione cycle in wheat varieties (Triticum aestivum L.) under arsenic stress.

The potential of arsenic (As) tolerant and sensitive varieties of wheat (Triticum aestivum L.) has yet to be explored despite of alarming situation of arsenic toxicity. To fill this gap, the study aimed to explore the role of antioxidants, phytochelatins, and ascorbate-glutathione for As tolerance in wheat. A total of eight varieties were exposed to different arsenate treatments (0, 1, 5, 10, 50, 100, 200, 500, 1000, 2000, and 10,000 µM) initially to screen effective treatment as well as contrasting varieties via Weibull distribution frequency for further analysis. The Weibull analysis found 200 µM as the most effective treatment in the present study. Selected varieties were analyzed for accumulation of total As and As speciation, oxidative stress (malondialdehyde, hydrogen peroxide), antioxidants (superoxide dismutase, catalase, peroxidase), phytochelatins, and ascorbate-glutathione cycle (glutathione-S-transferase, glutathione reductase, glutathione peroxidase, ascorbate peroxidase). Tolerant varieties showed less accumulation and translocation of total As, arsenate, and arsenite to the shoots compared with sensitive varieties under 200 µM treatment. Low concentration in tolerant varieties correlated with better growth and development response. Tolerant varieties showed higher induction of metabolites (glutathione, phytochelatins) compared to sensitive ones. Furthermore, tolerant varieties showed better performance of antioxidant and ascorbate-glutathione cycle enzymes in response to As exposure. The findings of the present study provided great insight into the wheat tolerance mechanism upon As exposure between contrasting varieties.

Identification of arsenic-tolerant varieties and candidate genes of tolerance in spring wheat (Triticum aestivum L.).

Despite the growing concerns about arsenic toxicity, information on tolerance and responsible genetic factors in wheat remains elusive. To address that, the present study aimed to screen the wheat varieties against arsenic based on growth parameters, yield, grain accumulation, and associated genes. A total of 110 wheat varieties were grown in arsenic-contaminated regions to record physio-morphological traits. The wheat 90K Infinium iSelect SNP array was used for the genome-wide association model to identify genomic regions. Wheat varieties such as Punjab-81, AARI-11, and Daman showed arsenic concentrations >45 µg/kg in similar conditions as well as the impact on grain yield, chlorophyll, Thousand Kernel Weight, and plant height. Contrastingly, varieties like Kohistan-97, As-2002, Barani-70, and Pari-73 showed grain concentrations <5 µg/kg grown under highly contaminated conditions. Three significant loci associated with arsenic accumulation in grain were identified on chromosomes 6A (qASG1-6A) and 6B (qASG3-6B and qASG4-6B). Annotation at these loci identified 39 wheat genes among which several were important for growth and tolerance against stress. The candidate gene (TraesCS6B02G429400) responsible for Glutathione-S-transferase was identified in the present study and must be investigated further using a transcriptomic approach. The present study provided background information for breeding prospects to improve wheat yield and tolerance against arsenic.

Arsenic and fluoride co-exposure through drinking water and their impacts on intelligence and oxidative stress among rural school-aged children of Lahore and Kasur districts, Pakistan.

Arsenic (As), and fluoride (F-) are potent contaminants with established carcinogenic and non-carcinogenic impacts on the exposed populations globally. Despite elevated groundwater As and F- levels being reported from various regions of Pakistan no biomonitoring study has been reported yet to address the co-exposure impact of As and F- among school children. We aimed to investigate the effects of these two contaminants on dental fluorosis and intelligence quotient (IQ) along with the induction of oxidative stress in rural children under co-exposed conditions. A total of 148 children (5 to 16 years old) from the exposed and control group were recruited in the current study from endemic rural areas of Lahore and Kasur districts, Pakistan having elevated As and F- levels in drinking water than permissible limits. We monitored malondialdehyde and its probable association with antioxidants activity (SOD, CAT, and GR) as a biomarker of oxidative stress. GSTM1/T1 polymorphisms were measured to find the impact of As on health parameters. Mean urinary concentrations of As (2.70 vs. 0.016 µg/L, P < 0.000) and F- (3.27 vs. 0.24 mg/L, P < 0.000) as well as the frequency of dental fluorosis were found elevated among the exposed group. The cases of children with lower IQ were observed high in the exposed group. Additionally, lower concentrations of antioxidants (SOD, CAT, and GR) were found suggesting high susceptibility to F- toxicity. The findings suggest that F- accounted for high variations in health parameters of children under the co-exposure conditions with As.

Pulmonary Dysfunction Augmenting Bacterial Aerosols in Leather Tanneries of Punjab, Pakistan.

BACKGROUND: Particulate matter-associated microbes in the workplace are a burning issue in occupational toxicology. Studies have reported on respiratory infections among tannery cohorts. This study uniquely presents measurements of airborne bacterial concentrations associated with varied particulate-matter sizes, their exposure, and consequent severity in occupational respiratory problems, all for different microenvironments within leather tanneries. METHODS: Analyses included molecular identification of isolates, computation of mass median aerodynamic diameter of aerosols, tannery process-exposure dose (TPED) to bacterial aerosols, and spirometry and symptom assessment of impaired pulmonary function. RESULTS: The highest bacterial concentrations were for rawhide treatment and finishing units, showing 3.6×103 and 3.7×103 CFU/m3, respectively. Identified bacterial species included Ochrobactrum pseudogrignonense, Neisseria bacilliformis, Enterobacter cloacae, Alcaligenes faecalis, Klebsiella pneumoniae, and Corynebacterium spp. Maximum and minimum values of mass median aerodynamic diameter were 8.3 µm and 0.65 µm for buffing and snuffing and production units, respectively. The highest TPED was 1,516.9 CFU/kg for finishing units. Respiratory symptoms in order of incidence were dyspnea > phlegm > cough > wheezing and tachypnea (equivalent). Bronchodilator measurements of FEV1, FVC, and PEF represent decline in lung function. Of 26 patients identified with COPD, most were working in rawhide treatment. CONCLUSION: We conclude that exposure-infection synergy is also a cause of pulmonary ailments and COPD development, rather than the better-known exposure-smoking synergy.

Heavy metal phyto-accretion, biochemical responses and non-carcinogenic human health risks of genetically diverse wheat genotypes cultivated with sewage of municipal origin.

Current study explored the effects of municipal sewage (MS) irrigation on heavy metal phyto-accretion, biochemical responses and human health risks of diverse wheat genotypes along with recycled municipal sewage (RMS). Mean concentrations of PO43-, NO3--N, chemical oxygen demand, biological oxygen demand, K, Co, Cu, Cd, Cr and Ni were found higher in MS than irrigation criteria. This led to significant increase in heavy metal contents in roots, stem and grains of MS irrigated wheat genotypes compared to RMS and control treatments. No adverse health risk effects for individual or multiple metals were recorded in RMS irrigated wheat genotypes on grounds of lowest heavy metal accumulation. Multivariate techniques i.e. principal component analyses (PCA) and hierarchical agglomerative cluster analyses (HACA) identified tolerant (inefficient metal accumulators) and sensitive (efficient metal accumulators) wheat genotypes in MS and RMS. Tolerant wheat genotypes showed lowest accumulation of heavy metals, efficient biochemical mechanisms to combat oxidative stress and lower health risks to adults/children. Cultivation of identified tolerant wheat genotypes is recommended in areas receiving municipal wastes to reduce human and environmental health risks. Moreover, genetic potential of identified tolerant wheat genotypes from MS and RMS can be utilized in breeding heavy metal tolerant wheat germplasm worldwide.

Fluorosis and cognitive development among children (6-14 years of age) in the endemic areas of the world: a review and critical analysis.

The fluoride contamination in water is still a live discussion among the scientific community, because of its beneficial and injurious health effects inflicted on the human population. The magnitude of groundwater fluoride contamination is aggravated by increasing anthropogenic activities. Groundwater is supposedly the main source through which people are highly exposed to fluoride, compared with other sources of exposure. Among human populations, fluoride-related health issues span from mild effects on teeth and bones to severe kidney problems, neurotoxicity, and even cancer. Nowadays, fluoride toxicity is gaining much attention in the endemic areas due to its adverse impact on the children's cognitive function, since children are more susceptible to fluoride toxicity as compared to adults. The primary mechanism behind the neurotoxicity of fluoride is still not clearly understood. However, knowingly, fluoride disrupts the biochemical mechanism and thus alters the normal functioning of the brain. Several human studies are suggestive of lowering children's IQ who was exposed to fluoride during their childhood. The conclusive findings of past research suggest that the fluoride concentration in potable water tends to grossly affect the children's IQ level. However, the body of proof is limited, because most of the studies are concentrated in few countries, and have their own limitations and data gaps. The grave implications of fluoride toxicity, therefore, demand extensive and properly designed research to bridging the data gap in developing countries. Furthermore, spanning research work across all the endemic areas of the world could generate larger database, helping resolve the issue on a large scale.

Transcriptome responses in blood reveal distinct biological pathways associated with arsenic exposure through drinking water in rural settings of Punjab, Pakistan.

BACKGROUND: Groundwater Arsenic (As) contamination is a global public health concern responsible for various health implications and a neglected area of environmental health research in Pakistan. Because of interindividual differences in genetic predisposition, As-related health issues may not be equally distributed among the As-exposed population. However, till date, no studies have been conducted including multiple SNPs involved in As metabolism and disease risk using a linear mixed effect model approach to analyze peripheral blood transcriptomics results. OBJECTIVES: In order to detect early responses on the gene expression level and to evaluate the impact of selected SNPs inferring disease risks associated with As exposure, we designed a systematic study to investigate blood transcriptomics profiles of 57 differentially exposed rural subjects living in drinking water As-contaminated settings of Lahore and Kasur districts in Punjab Province in southeast Pakistan. Exposure among the subjects was correlated with individual transcriptome responses applying urinary As profiles as the main biomarker for risk stratification. METHODS: We performed whole genome gene expression analysis in blood of subjects using microarrays. Linear effect mixed models were applied for evaluating the combined impact of SNPs hypothetically increasing the risk for As exposure-induced health effects (GSTM1, GSTT1, As3MT, DNMT1, MTHFR, ERCC2 and EGFR). RESULTS: Our findings confirmed important signaling, growth factor, cancer and other disease related pathways known to be associated with increased As exposure levels. In addition, upon implementing our integrative SNPs-based genetic risk factor, pathways associated with an increased risk of NAFLD and diabetes appeared significantly enhanced by down-regulation of genes NDUFV3, IKBKB, IL6R, ADIPOR1, PPARA, OGT and FOXO1. CONCLUSION: We report the first comprehensive study applying state-of-the-art bioinformatics approaches to address multiple SNP-based inter-individual variability in adverse molecular responses among subjects exposed to drinking water As contamination in Pakistan thereby providing strong evidence of various gene expression targets associated with development of known As-related diseases.

Insight into occurrence, profile and spatial distribution of organochlorine pesticides in soils of solid waste dumping sites of Pakistan: Influence of soil properties and implications for environmental fate.

Waste dumping sites are considered as significant disposal pathway for waste contaminants including pesticides. In the present study OCPs were analyzed in soils of waste dumping sites of Pakistan. The mean concentrations of OCPs were in the order: ∑DDTs>∑HCHs>∑Endosulfan>∑HCB>Heptachlor. Order of overall ∑OCPs contamination with respect to location was Lahore>Sukkur>Karachi>Kamoki>Faisalabad>Hyderabad>Losar>Gujrat>Peshawar. Distribution of OCPs in solid waste dumping site was mainly influenced by textural classes, input history and pollution source. Soil texture was the dominant factor for retention of OCPs, whereas TOC and black carbon has not significantly impacted the concentrations of OCPs. Diagnostic ratios indicated the historical input, anaerobic degradation pathway and use of technical mixtures of DDTs in majority of waste dumping sites whereas for HCHs recent as well as past usage of technical mixture was prevalent in most of the areas. Regression analysis revealed a weak positive correlation of OCPs with socioeconomic indices (HDI, Population, waste generation) which is linked with history of use of these contaminants in the respective areas. Forecasted waste generation quantity for the year 2026 showed that waste generation amount will get doubled by the year 2026 suggesting the need properly designed waste management system.

Assessing residual status and spatial variation of current-use pesticides under the influence of environmental factors in major cash crop growing areas of Pakistan.

The status of seven currently used pesticides were assessed under the influence of soil parameters in surface soils of cash crop growing areas of Pakistan. Chlorpyrifos occurred in highest mean concentration (1.18 mg kg-1). Selected pesticides exhibited higher affinity towards both organic carbon and black carbon fractions. The δ13C stable carbon isotopic fraction of inorganic carbon was also used as a tracer and disclosed high retention of total organic carbon in Swat and Swabi sites. Statistical analysis revealed that carbon storage was primarily influenced by altitude and temperature. Soil clay mineral oxides of aluminum and iron positively correlated with organic carbon and selected pesticides (chlorpyrifos and cyprodinil). Soil to plant bio-concentration ratios predicted heightened uptake of azinfos and diazinon in major cash crop bio mass. Occupational risk via soil ingestion expressed no significant threat to the farmer community.

Accounting for water levels and black carbon-inclusive sediment-water partitioning of organochlorines in Lesser Himalaya, Pakistan using two-carbon model.

This study was designed to monitor organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) in riverine water of Lesser Himalaya along the altitude. Further, the sediment-water partitioning employing organic carbon and black carbon models were assessed. Results revealed higher water levels of organochlorine pesticides (0.07-41.4 ng L-1) and polychlorinated biphenyls (0.671-84.5 ng L-1) in Lesser Himalayan Region (LHR) of Pakistan. Spatially, elevated levels were observed in the altitudinal zone (737-975 masl) which is influenced by anthropogenic and industrial activities. Sediment-water partitioning of OCPs and PCBs were deduced using field data by employing one-carbon (fOCKOC) and two-carbon Freundlich models (fOCKOC + fBCKBCCWnF-1). Results suggested improved measured vs predicted model concentrations when black carbon was induced in the model and suggested adsorption to be the dominant mechanism in phase partitioning of organochlorines in LHR.

Occupational exposure and consequent health impairments due to potential incidental nanoparticles in leather tanneries: An evidential appraisal of south Asian developing countries.

The incidental nanoparticles' (INPs) emission at work and the consequent health impairments is a burning issue of occupational toxicology. The present study is a thorough review of available literature marking an assortment of indicators on INPs generation at leather tanneries and measurable occupational ailments. The literature reported evidences unleash a similarity between the mechanisms of leather tannery induced health damages and toxico-kinetics of incidental nanoparticles in human body. The data on physico-chemical characterization of leather tannery surface dust presents presence of stressors like heavy metals, microbes, animal fur and fibers along with organic and inorganic chemicals. Bearing same characteristics, the mechanism of INPs' induced toxicity (inflammation, increased reactive oxygen species and permeability of blood brain barrier), major target organs (lung, heart, brain, skin and liver) and health damages (cancer, DNA damage, blood coagulation, cardiac arrest, platelet alteration) are quite similar to those found among tannery workers. This review also presents the identification of the different types of potential INPs production and process sources in leather tanneries. There is no data found on Particulate size variation and consequent disparity of these characterizations has been established. However, the reported literature furnishes evidences which support the premise that there is a dire need of size based incidental particulates investigation with a special emphasis on nanoparticles.

Elucidating the urban levels, sources and health risks of polycyclic aromatic hydrocarbons (PAHs) in Pakistan: Implications for changing energy demand.

Due to the severe fuel crisis in terms of natural gas, a paradigm shift in fuel combustion (diesel, gasoline, and biomass) may increase the atmospheric emissions and associated health risks in Pakistan. Present study was aimed to investigate the concentration of fugitive PAHs in the environment (outdoor and indoor settings), associated probabilistic health risk assessment in the exposed population, and possible linkage between fuel consumption patterns and PAHs emissions in twin cities (Rawalpindi and Islamabad) of Pakistan. Results showed that the mean PAHs concentrations (air: 2390pgm-3; dust: 167ngg-1) in the indoor environment were higher than that of the outdoor environment (air: 2132pgm-3; dust: 90.0ngg-1). Further, the source apportionment PCA-MLR receptor model identified diesel and gasoline combustion as the primary PAHs sources in the urban and sub-urban settings. Estimated life cancer risk (LCR) potential via inhalation to indoor PAHs was higher with a probability of 2.0 cases per 10,000 inhabitants as compared to outdoor exposure. Incremental lifetime cancer risk (ILCR) model from exposure to dust bound PAHs showed risk in the order of ingestion>dermal>inhalation for various exposure pathways. Likewise, estimated daily intake (EDI) model reflects that PAHs in surface dust enter into the human body mainly through the respiratory system because EDI for breathing was reported higher than that of oral intake. Therefore, adoption of sustainable fuels is recommended to meet the energy requirements and to reduce PAHs emissions and related health risks in the twin cities of Pakistan.

Role of black carbon in soil distribution of organochlorines in Lesser Himalayan Region of Pakistan.

Black carbon and total organic carbon (TOC) along with organochlorines (OCs) were analyzed in soils from four sampling zones of Lesser Himalayan Region based on source proximity/anthropogenic influences along the altitude. CTO-375 method was used for BC analysis while OCs were analyzed by GC-MS/MS system. BC and TOC ranged between 0.16-1.77 and 6.8-41.3 mg g-1 while those of OCPs and PCBs ranged between 0.69 and 5.77 and 0.12-2.55 ng g-1, respectively. ∑DDTs were the dominant (87.9%) among OCPs while tri- and tetra- (65.5%) homologue groups among PCBs. Hexa-PCBs, however also showed higher contribution (20.4%) in the region. Source diagnostic ratios of DDE + DDD/DDT (0.1-1.53) indicated both fresh and old input while α-HCH/γ-HCH (0.19-2.49) showed presence of lindane in the region. Higher concentration of OCs were observed in Zone C at altitudinal range of 737-975 masl that are close to the human influences and potential sources of POPs. The results of linear regression analysis revealed potential input of BC in soil distribution of OC concentrations in the region.

Higher atmospheric levels and contribution of black carbon in soil-air partitioning of organochlorines in Lesser Himalaya.

Due to influence of wind patterns (monsoon and westerlies) and anthropogenic activities, lower stretch of Himalaya is at direct exposure to persistent organic pollutants (POPs). Current study was designed to monitor atmospheric concentrations of long lived organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) using polyurethane passive air sampling in the Lesser Himalayan Region (LHR) of Pakistan. Levels of ∑HCHs, ∑DDTs and ∑PCBs were observed in a range between 3 and 210 pg m-3, 0.75-67.1 pg m-3 and 8.49-458 pg m-3, respectively. Though, air mass trajectories over LHR indicated long range transport as atmospheric source input which was further explained by Clausius-Clapeyron plots between ln P and inverse of temperature (1000/T; K) where all OCPs and most of the PCBs have shown insignificant relationship (r2 = 5E-06-0.41; p-value = 0.06-0.995). However, local source emissions and valley transport may also implicate based on spatial distribution and altitudinal patterns. Additionally, soil-air partitioning of organochlorines was assessed using octanol-air partition (KOA) and black carbon-air partition (KBC) based models. Regression results indicated combined influence of both organic matter (r2 = 0.298-0.85) and black carbon (r2 = 0.31-0.86) via absorption and adsorption, respectively in soil-air partitioning of OCs in LHR. This paper sheds light on the atmospheric concentrations of OCs and help in better understanding of the processes involved in fate and transport of organic pollutants in Himalayan region. Further investigations are required to understand the role of carbon moieties in fate and transport of other groups of organic pollutants at higher altitudes of Himalayan region.

Pesticides contaminated dust exposure, risk diagnosis and exposure markers in occupational and residential settings of Lahore, Pakistan.

There are few studies documenting the dust loaded with pesticides as a potential non-dietary exposure source for occupational worker and populations living near agricultural farms and pesticides formulation plants. In present study we have evaluated the pesticide concentration in dust from potential sites and relevant health risk from dust ingestion. Furthermore, the effect of currently used pesticides was investigated on blood and urine parameters of subjects: farmer, factory worker, urban resident and rural resident and controlled subjects with presumably different levels of exposure. The urinary metabolites (TCPY and IMPY) were quantified as biomarkers of exposure to chlorpyrifos and diazinon in relation with biomarkers of effect including BuChE, LH, FSH, testosterone and oxidative stress. Results showed that chlorpyrifos and diazinon were present in higher concentration in dust and posed a high health risk to exposed subjects. The mean SOD value was high among the farmer (3048U/g Hb) followed by factory worker (1677.6U/g Hb). The urinary biomarkers - TCPY and IMPY- were found higher in exposed subjects as compared to control. Furthermore, testosterone was found in higher concentration in factory worker than control (12.63ng/ml vs 4.61ng/ml respectively). A decreased BuChE activity was noticed in occupational group and significant differences were observed in control verses exposed subjects. The PCA analysis evidenced the impact of pesticides on exposure biomarkers and male reproductive hormones. The study suggests that dust contaminated with pesticides engenders significant health risk particularly related to the nervous and endocrine system, not only for occupational workers exposed to direct ingestion but also for nearby residential community. Succinctly putting: Pesticides loaded dust in the city of Lahore, being a high priority concern for the government of Pakistan, demands to be addressed.

Potential health risk of heavy metals in the leather manufacturing industries in Sialkot, Pakistan.

This is a systematical report on the potential health risk of heavy metals from the leather industries in Pakistan based on multiple biological matrices of the exposed workers and indoor dust samples. The adverse impacts of heavy metals on the oxidative enzyme and their risks to workers' health were also explored. Our results indicated that the level of Cr in indoor industrial dust was more than twice, compared to the background household dust. Blood, urine and hair samples of exposed workers showed significantly high concentrations of heavy metals, compared to those in the control group. Superoxide dismutase (SOD) level in the blood samples expressed significant positive correlation with Cr and Ni. Total hazard quotients (HQs)/hazard index (HI) were >1, and Cr (VI) exhibited higher cancer risks than that of Cd in the exposed workers. In addition, the PCA-MLR analysis confirmed that the industrial sections; cutting, shivering/crusting, and stitching were the principal contributors of heavy metals in the biological entities of the workers. Taken together, our results highlighted the occupationally exposed groups would likely to experience the potential health risks due to excessive exposure to the heavy metals from the leather industries.

Health hazards of child labor in the leather products and surgical instrument manufacturing industries of Sialkot, Pakistan.

Child labor is a major challenge in the developing countries and comprehensive health hazard identification studies on this issue are still lacking. Therefore, the current study is an effort to highlight the health concerns of child labor exposed in the key small scale industries of Sialkot, Pakistan. Our findings revealed jolting levels of heavy metals in the urine, blood, serum, saliva, and hair samples collected from the exposed children. For example, in the urine samples, Cd, Cr, Ni, and Pb were measured at the respective concentrations of 39.17, 62.02, 11.94 and 10.53 µg/L in the surgical industries, and 2.10, 4.41, 1.04 and 5.35 µg/L in the leather industries. In addition, source apportionment revealed polishing, cutting, and welding sections in the surgical industries and surface coating, crusting, and stitching sections in the leather industries were the highest contributors of heavy metals in the bio-matrices of the exposed children, implying the dusty, unhygienic, and unhealthy indoor working conditions. Further, among all the bio-matrices, the hair samples expressed the highest bioaccumulation factor for heavy metals. In accordance with the heavy metal levels reported in the exposed children, higher oxidative stress was found in the children working in the surgical industries than those from the leather industries. Moreover, among heavy metals' exposure pathways, inhalation of industrial dust was identified as the primary route of exposure followed by the ingestion and dermal contact. Consequently, chemical daily intake (CDI), carcinogenic and non-carcinogenic hazard quotients (HQs) of heavy metals were also reported higher in the exposed children and were also alarmingly higher than the corresponding US EPA threshold limits. Taken all together, children were facing serious health implications in these industries and need immediate protective measures to remediate the current situation.

Tracing biomarker of PAH-exposure and susceptibility factor (GSTM-polymorphism) among cancer patients in Pakistan.

We studied cancer patients for possible PAH exposure, using urinary concentration of 1-hydroxypyrene (1-OHP) as a biomarker of internal dose of polycyclic aromatic hydrocarbons (PAHs). The subjects included in this study belonged to various socio-demographic backgrounds, and were diagnosed with cancer (i.e. lung, head and neck or digestive tract cancer). In general, we observed high concentration of urinary 1-OHP among digestive tract cancer patients, compared with the controls (CN) (mean 1.06, median 1.03 and mean 0.62, median 0.63 µmol/mol-Cr in digestive tract cancer patients and controls respectively). The concentrations of urinary 1-OHP were higher than the background level of PAHs; therefore, these groups could have been exposed to PAHs. Highest urinary 1-OHP concentration was observed in digestive tract cancer patients (median 1.25 µmol/mol-Cr) with GSTM-1 genotype. The results of PCA were consistent with qualitative and quantitative data analysis. The contribution of urinary 1-OHP eigenvector revealed a relatively high PAH-exposure among cancer patients compared with CN, while diet and age were influential parameters among cancer patients, which could have a strong link in cancer etiology in the selected exposure groups.

Effects of structurally different noncoplanar and coplanar PCBs on HELF cell proliferation, cell cycle, and potential molecular mechanisms.

Polychlorinated biphenyls (PCBs) are a group of chemicals that persist in the environment, indoors, and humans. Lung exposure to airborne and food contaminants, such as PCBs, may cause possible lung disorders, such as cancer. In the present study, we investigated the effects of structurally different lower chlorinated (≤4Cl), noncoplanar PCB40, and coplanar PCB77 on human lung fibroblast cell line (HELF) cell proliferation, cell cycle progression, and possible molecular mechanisms. Noncoplanar PCB40 and coplanar PCB77 exhibited concentration- and time-dependent biphasic dose-response effects on HELF cell proliferation. Noncoplanar PCB40 and coplanar PCB77 induced 23 and 45% cytotoxicity at higher concentrations than the control. The flow cytometry analysis showed that exposure to PCB40 caused a significant increase in time spent in the G1 phase but decreased length of the S phase in a concentration- and time-dependent manner, whereas PCB77 exposure decreased time spent in the G1 and S phases but increased time spent in the G2 phase. Western blot analysis indicated that PCB77 increased the expression of cyclin E, CDK2, p21, and caspase-9, while PCB40 decreased the expression of these proteins (except CDK2 and p21). An increase in CDK expression after exposure to PCB77 suggests that it may cause carcinogenic effects on HELF cells at higher doses. Our results also demonstrate that the different cytotoxic effects induced by coplanar and nonplanar PCBs were correlated with their structural characteristics; the coplanar congener was more cytotoxic than the nonplanar congener. The study elaborates threshold levels for these chemicals and suggests that the cytotoxicity mechanisms by which PCB congeners act on HELF cells depend on their planarity and chemical structures. Furthermore, the study will be important for developing antidotes to the adverse effects and risk assessment practices for PCBs. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1183-1190, 2017.

Toxicity and oxidative stress induced by chromium in workers exposed from different occupational settings around the globe: A review.

The present review focused on the levels and toxicological status of heavy metals especially chromium (Cr) in the exposed workers from different occupational settings around the globe and in Pakistan. It was found that exposed workers from leather tanning and metal plating units showed elevated levels of Cr than the workers from other occupational settings. Cr and other heavy metals level in biological matrices of the exposed workers in different occupational settings revealed that developing countries are severely contaminated. Occupational settings from the Sialkot district, Pakistan exhibited elevated level of Cr in biological entities of the exposed workers. Review suggested that higher level of Cr exposure to the workers enhance the oxidative stress (reactive oxygen species (ROS) and hydroxyl (OH) radical generation) which may cause; cellular and molecular damage such as genotoxicity and chromosomal aberration formations, and carcinogenic effects. This review will help to understand the Cr contamination mechanisms and associated health implications in different occupational settings around the globe in general and particularly to Pakistan. This study will also assist occupational health and safety management authorities to devise or change the Cr recommended exposure limits (REL) for different occupational settings.