Occupational exposure to benzene and mortality risk of lymphohaematopoietic cancers in the Swiss National Cohort.

OBJECTIVES: Previous studies established a causal relationship between occupational benzene exposure and acute myeloid leukemia (AML). However, mixed results have been reported for associations between benzene exposure and other myeloid and lymphoid malignancies. Our work examined whether occupational benzene exposure is associated with increased mortality from overall lymphohaematopoietic (LH) cancer and major subtypes. METHODS: Mortality records were linked to a Swiss census-based cohort from two national censuses in 1990 and 2000. Cases were defined as having any LH cancers registered in death certificates. We assessed occupational exposure by applying a quantitative benzene job-exposure matrix (BEN-JEM) to census-reported occupations. Exposure was calculated as the products of exposure proportions and levels (P × L). Cox proportional hazards models were used to calculate LH cancer death hazard ratios (HR) and 95% confidence intervals (CI) associated with benzene exposure, continuously and in ordinal categories. RESULTS: Our study included approximately 2.97 million persons and 13 415 LH cancer cases, including 3055 cases with benzene exposure. We observed increased mortality risks per unit (P × L) increase in continuous benzene exposure for AML (HR 1.03, 95% CI 1.00-1.06) and diffuse large B-cell lymphoma (HR 1.09, 95% CI 1.04-1.14). When exposure was assessed categorically, increasing trends in risks were observed with increasing benzene exposure for AML (P=0.04), diffuse large B-cell lymphoma (P=0.02), and follicular lymphoma (P=0.05). CONCLUSION: In a national cohort from Switzerland, we found that occupational exposure to benzene is associated with elevated mortality risks for AML, diffuse large B-cell lymphoma, and possibly follicular lymphoma.

The burden of disease attributable to indoor air pollutants in China from 2000 to 2017.

BACKGROUND: High-level exposure to indoor air pollutants (IAPs) and their corresponding adverse health effects have become a public concern in China in the past 10 years. However, neither national nor provincial level burden of disease attributable to multiple IAPs has been reported for China. This is the first study to estimate and rank the annual burden of disease and the financial costs attributable to targeted residential IAPs at the national and provincial level in China from 2000 to 2017. METHODS: We first did a systematic review and meta-analysis of 117 articles from 37 231 articles identified in major databases, and obtained exposure-response relationships for the candidate IAPs. The exposure levels to these IAPs were then collected by another systematic review of 1864 articles selected from 52 351 articles. After the systematic review, ten IAPs with significant and robust exposure-response relationships and sufficient exposure data were finally targeted: PM2·5, nitrogen dioxide, sulphur dioxide, ozone, carbon monoxide, radon, formaldehyde, benzene, toluene, and p-dichlorobenzene. The annual exposure levels in residences were then evaluated in all 31 provinces in mainland China continuously from 2000 to 2017, using the spatiotemporal Gaussian process regression model to analyse indoor originating IAPs, and the infiltration factor method to analyse outdoor originating IAPs. The disability-adjusted life-years (DALYs) attributable to the targeted IAPs were estimated at both national and provincial levels in China, using the population attributable fraction method. Financial costs were estimated by an adapted human capital approach. FINDINGS: From 2000 to 2017, annual DALYs attributable to the ten IAPs in mainland China decreased from 4620 (95% CI 4070-5040) to 3700 (3210-4090) per 100 000. Nevertheless, in 2017, IAPs still ranked third among all risk factors, and their DALYs and financial costs accounted for 14·1% (95% CI 12·3-15·6) of total DALYs and 3·45% (3·01-3·82) of the gross domestic product. Specifically, the rank of ten targeted IAPs in order of their contribution to DALYs in 2017 was PM2·5, carbon monoxide, radon, benzene, nitrogen dioxide, ozone, sulphur dioxide, formaldehyde, toluene, and p-dichlorobenzene. The DALYs attributable to IAPs were 9·50% higher than those attributable to outdoor air pollution in 2017. For the leading IAP, PM2·5, the DALYs attributable to indoor origins are 18·3% higher than those of outdoor origins. INTERPRETATION: DALYs attributed to IAPs in China have decreased by 20·0% over the past two decades. Even so, they are still much higher than those in the USA and European countries. This study can provide a basis for determining which IAPs to target in various indoor air quality standards and for estimating the health and economic benefits of various indoor air quality control approaches, which will help to reduce the adverse health effects of IAPs in China. FUNDING: The National Key Research and Development Program of China and the National Natural Science Foundation of China.

Benzene, 1,2,4-Trimethoxy-5-(2-Methyl-1-Propen-1-yl) Attenuates D-galactose/AlCl3-induced Cognitive Impairment by Inhibiting Inflammation, Apoptosis, and improving Expression of Memory-Related Proteins.

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by decreased learning ability and memory deficits. Our previous findings suggested that benzene, 1,2,4-trimethoxy-5-(2-methyl-1-propen-1-yl) (BTY) can ameliorate the dysfunction of GABAergic inhibitory neurons associated with neurological diseases. On this basis, we investigated the neuroprotective effect of BTY on AD and explored the underlying mechanism. This study included in vitro and in vivo experiments. BTY could maintain cell morphology, improve cell survival rate, reduce cell damage, and inhibit cell apoptosis in vitro experiments. Further, BTY has good pharmacological activity in vivo experiments, of which behavioral experiments showed that BTY could improve AD-like mice's learning and memory abilities. Besides, histopathological experiments indicated that BTY could maintain the morphology and function of neurons, reduce amyloid ß-protein 42 (Aß42) and phosphorylated tau (p-tau) accumulation, and decrease the levels of inflammatory cytokines. Finally, western blot experiments showed that BTY could inhibit the expression of apoptosis-related proteins and promote the expression of memory-related proteins. In conclusion, this study indicated that BTY may be a promising drug candidate for AD.

Residential proximity to petrol stations and risk of childhood leukemia.

Petrol stations emit benzene and other contaminants that have been associated with an increased risk of childhood leukemia. We carried out a population-based case-control study in two provinces in Northern Italy. We enrolled 182 cases of childhood leukemia diagnosed during 1998-2019 and 726 age- and sex-matched population controls. We geocoded the addresses of child residences and 790 petrol stations located in the study area. We estimated leukemia risk according to distance from petrol stations within a 1000 m buffer and amount of supplied fuel within a buffer of 250 m from the child's residence. We used conditional logistic regression models to approximate risk ratios (RRs) and 95% confidence intervals (CIs) for associations of interest, adjusted for potential confounders. We also modeled non-linear associations using restricted cubic splines. In secondary analyses, we restricted to acute lymphoblastic leukemia (ALL) cases and stratifed by age (<5 and ≥5 years). Compared with children who lived≥1000 m from a petrol station, the RR was 2.2 (95% CI 0.5-9.4) for children living<50 m from nearest petrol station. Associations were stronger for the ALL subtype (RR=2.9, 95% CI 0.6-13.4) and among older children (age≥5 years: RR=4.4, 95% CI 0.6-34.1; age<5 years: RR=1.6, 95% CI 0.1-19.4). Risk of leukemia was also greater (RR=1.6, 95% CI 0.7-3.3) among the most exposed participants when assigning exposure categories based on petrol stations located within 250 m of the child's residence and total amount of gasoline delivered by the stations. Overall, residence within close proximity to a petrol station, especially one with more intense refueling activity, was associated with an increased risk of childhood leukemia, though associations were imprecise.

Environmental and occupational exposure among cancer patients in Mato Grosso, Brazil.

OBJECTIVE: To estimate the prevalence of occupational and environmental exposure according to sociodemographic factors in cancer patients treated at reference hospitals in the state of Mato Grosso, Brazil. METHODS: This is a cross-sectional study on cancer patients aged 18 years or older. The prevalence of exposure to pesticides, asbestos, lead, heavy metals, formaldehyde, benzene, exposure to industrial dust, and handling of other chemical substances were calculated according to sex, age group, and level of education. RESULTS: A total of 1,012 patients were interviewed (55.0% women, 45.6% aged 60 years or older, and 56.8% had less than five years of formal education). Pesticides (22.8%), industrial dust (10.7%), and benzene (10.1%) were the most frequent exposures. Occupational and environmental exposure was higher in men for all evaluated exposures, except for formaldehyde, which was higher in women. Exposure to pesticides, industrial dust, benzene, asbestos, and heavy metals increased with age and were more frequent among those with lower level of education. CONCLUSION: Approximately one in five cancer patients treated at reference hospitals in Mato Grosso reported having been exposed to pesticides, and one in ten were exposed to industrial dust and benzene, with greater exposure among men, older individuals, and those with lower level of education.

Genetic variations in ATM and H2AX loci contribute to risk of hematological abnormalities in individuals exposed to BTEX chemicals.

BACKGROUND: Loci controlling DNA double-strand breaks (DSBs) repair play an important role in defending against the harmful health effects of benzene, toluene, ethylbenzene, and xylene (BTEX), but their gene variants may alter their repair capacity. The aim of the current study was to determine the relationship of functional polymorphisms ATM-rs228589 A>T, WRN-rs1800392 G>T and H2AX-rs7759 A>G in DBS repair loci with the abnormal hematological indices in workers who exposed to BTEXs. METHODS: We included 141 cases with one or more abnormal hematological parameters, who had been occupationally exposed to BTEX chemicals and 152 controls with a similar exposure condition but without any abnormal hematological parameters. Atmospheric concentrations of BTEXs were measured and whole blood samples were taken from the participants to determine hematologic parameters and SNP genotyping. RESULTS: Results showed that T allele of ATM-rs228589 and G allele of H2AX-rs7759 had a higher frequency in cases than controls (p = 0.012 and p = 0.001, respectively). Also, AT and TT genotypes of ATM-rs228589 and AG and GG genotypes of H2AX-rs7759 were higher in cases compared to controls. The AT and TT genotypes of ATM-rs228589 have significant associations with a risk of hematological abnormalities in the codominant (AT vs. AA, p = 0.018), dominant (AT + TT vs. AA, p = 0.010) and overdominant (AT vs. AA + TT, p = 0.037) models. The GG and AG genotypes of H2AX-rs7759 were in relation with increased risk of abnormal hematological indices under codominant (GA vs. AA, p = 0.009 & GG vs. AA, p = 0.005), dominant (AG + GG vs. AA, p = 0.001), and recessive (GG vs. AA + AG, p = 0.025) models. CONCLUSIONS: These observations may help to understand the mechanisms of BTEX hematotoxicity and identify useful biomarkers of risk assessment for workers exposed to BTEX.

A 4-Benzene-Indol Derivative Alleviates LPS-Induced Acute Lung Injury Through Inhibiting the NLRP3 Inflammasome.

Acute lung injury (ALI) is a common complication of critical illness that could frequently lead to acute respiratory distress syndrome and other serious clinical consequences. Sepsis is one of the major and most common inducements among all causes of ALI. Due to its high incidence and mortality rate and also the complexity in treatment, sepsis-related ALI has become an urgent clinical problem waiting to be solved effectively. At present, only the protective ventilation strategy, restrictive fluid management, and antibiotics application are measures that can improve the prognosis with evidence-based medical proof. No pharmacological treatment is currently available to protect or significantly reverse the prognosis. Seeking for effective interventions measures for sepsis-related ALI is one of the most necessitous research directions. In this research, a conspicuous discovery of treatment-related translational use for a 4-benzene-indol derivative was elaborated by screening a large number of chemical compounds. The results showed that 4-benzene-indol derivative could not only suppress the activation of NLRP3 inflammasome both in vitro and alleviate LPS-induced ALI in vivo but also suppress the NLRP3 inflammasome in human myeloid leukemia mononuclear cells (THP-1) cell lines. Mechanistically, 1,2-diol blocks the NLRP3 inflammasome activation by disrupting NLRP3-NEK7 interaction and the subsequent NLRP3 inflammasome assembly and activation. To summarize, this research indicated that the newly-discovered 4-benzene-indol derivative targets NLRP3 inflammasome signaling, which consequently alleviates sepsis-related ALI. Collectively, the 4-benzene-indol derivative may serve as a potential therapeutic drug and NLRP3 inflammasome signaling would be a novel pharmaceutical target for clinical treatment of sepsis-related ALI.

[Concentration Analysis and Health Risk Assessment of Air Pollutants in Newly Decorated Public Places in Xi'an].

In order to understand the levels of indoor air pollution and health risks in public places, our research group conducted air quality monitoring and human health risk assessments for five types of public places (offices, classrooms, laboratories, banks, and hospitals) in Xi'an City from December 2017 to July 2020. The test items included formaldehyde, benzene, toluene, xylene, n-butyl acetate, ethylbenzene, styrene, n-undecane, and total volatile organic compounds (TVOC). The results showed that formaldehyde had the highest exceedance rate (59.4%), followed by toluene, TVOC, benzene, and xylene. Among the five types of public places, hospitals had the highest rate of pollutants exceeding the standard (46.7%), and the main pollutants exceeding the standard were formaldehyde, benzene, and toluene. The results showed that the concentrations of formaldehyde and TVOC were positively correlated with temperature and humidity. The health risk assessment results showed that there were carcinogenic risks of formaldehyde and benzene in different places; people working in banks had a higher risk of formaldehyde carcinogenesis, and those working in hospitals had a higher risk of benzene carcinogenesis. This study provides a reference for the level of indoor air pollution in public places in Xi'an City, and is of great significance to the health risk research of related populations.

Ambient BTEX exposure and mid-pregnancy inflammatory biomarkers in pregnant African American women.

Air pollution is associated with preterm birth (PTB), potentially via inflammation. We recently showed the mixture benzene, toluene, ethylbenzene, and xylene (BTEX) is associated with PTB. We examined if ambient BTEX exposure is associated with mid-pregnancy inflammation in a sample of 140 African-American women residing in Detroit, Michigan. The Geospatial Determinants of Health Outcomes Consortium study collected outdoor air pollution measurements in Detroit; these data were coupled with Michigan Air Sampling Network measurements to develop monthly BTEX concentration estimates at a spatial density of 300 m2. First trimester and mid-pregnancy BTEX exposure estimates were assigned to maternal address. Mid-pregnancy (mean 21.3 ± 3.7 weeks gestation) inflammatory biomarkers (high-sensitivity C-reactive protein, interleukin [IL]-6, IL-10, IL-1ß, and tumor necrosis factor-α) were measured with enzyme immunoassays. After covariate adjustment, for every 1-unit increase in first trimester BTEX, there was an expected mean increase in log-transformed IL-1ß of 0.05 ± 0.02 units (P = 0.014) and an expected mean increase in log-transformed tumor necrosis factor-α of 0.07 ± 0.02 units (P = 0.006). Similarly, for every 1-unit increase in mid-pregnancy BTEX, there was a mean increase in log IL-1ß of 0.06 ± 0.03 units (P = 0.027). There was no association of either first trimester or mid-pregnancy BTEX with high-sensitivity C-reactive protein, IL-10, or IL-6 (all P > 0.05). Ambient BTEX exposure is associated with inflammation in mid-pregnancy in African-American women. Future studies examining if inflammation mediates associations between BTEX exposure and PTB are needed.

Genomic analysis of mutations in platelet mitochondria in a case of benzene-induced leukaemia: A case report.

INTRODUCTION: As a hematopoietic carcinogen, benzene induces human leukemia through its active metabolites such as benzoquinone, which may cause oxidative damage to cancer-related nuclear genes by increasing reactive oxygen species (ROS). Mitochondrion is the main regulatory organelle of ROS, genetic abnormality of mitochondrion can impede its regulation of ROS, leading to more severe oxidative damage. Mutations have been related to certain types of cancer in several mitochondrial genes, but they have never been completely analyzed genome-wide in leukemia. PATIENT CONCERNS: The patient was a 52-year-old female who had chronic exposure to benzene for several years. Her symptoms mainly included recurrent dizziness, fatigue, and they had lasted for nearly 8 years and exacerbated in recent weeks before diagnosis. DIAGNOSIS: Samples of peripheral blood were taken from the patient using evacuated tubes with EDTA anticoagulant on the second day of her hospitalization. At the same time blood routine and BCR/ABL genes of leukemic phenotype were tested. Platelets were isolated for mitochondrial DNA (mtDNA) extraction. The genetic analysis of ATP synthase Fo subunit 8 (complex V), ATP synthase Fo subunit 6 (complex V), cytochrome c oxidase subunit 1 (complex IV), cytochrome c oxidase subunit 2 (complex IV), cytochrome c oxidase subunit 3, Cytb, NADH dehydrogenase subunit 1 (complex I) (ND) 1, ND2, ND3, ND4, ND5, ND6, 12S-RNA, 16S-RNA, tRNA-Cysteine, A, N, tRNA-Leucine, E, displacement loop in platelet mtDNA were performed. All the detected gene mutations were validated using the conventional Sanger sequencing method. INTERVENTIONS: The patient received imatinib, a small molecule kinase inhibitor, and symptomatic treatments. OUTCOMES: After 3 months treatment her blood routine test indicators were restored to normal. CONCLUSION: A total of 98 mutations were found, and 25 mutations were frame shift. The ND6 gene mutation rate was the highest among all mutation points. Frame shifts were identified in benzene-induced leukemia for the first time. Many mutations in the platelet mitochondrial genome were identified and considered to be potentially pathogenic in the female patient with benzene-induced leukemia. The mutation rate of platelet mitochondrial genome in the benzene-induced leukemia patient is relatively high, and the complete genome analysis is helpful to fully comprehend the disease characteristics.

[Campaign of labour inspections on the implementation of protection measures against carcinogenic agents in fuel station workers]. / Piano di vigilanza sul rispetto degli obblighi in materia di protezione dagli agenti cancerogeni dei lavoratori addetti alla distribuzione carburanti.

SUMMARY: Following the reduction in levels of exposure to benzene over the last few decades, the cancer risk of refuelers currently represents an occupational hygiene issue potentially underestimated by employers and workers themselves. Based on the literature data, the occurrence of adverse effects of neoplastic nature can not actually be excluded in this professional category, since it is not possible to define a threshold dose. In the period 2016 - 2019, an extensive focused campaign of labour inspections was conducted in the province of Bari by the OSH inspection services of the Health Local Authority in order to verify the compliance with the legislation on the workers' protection from carcinogenic agents at fuel stations. In particular, the obligations referring risk assessment, workplace hygiene, environmental monitoring, personal protective equipment (PPE), health surveillance, biological monitoring and recording of exposure to carcinogens were verified. Although these obligations were documentarily fulfilled by almost all the 162 plants inspected in the province of Bari, several critical issues were found in the approach to carcinogenic risk, including, more frequently, the lack of suitable changing rooms with relative lockers for clothing, the scarce use of gloves when dispensing fuel, the absence or incompleteness of the carcinogenic risk assessment documents, the failed or incorrect execution of biological monitoring. Data of the environmental monitoring carried out by the companies confirm that the current exposures to benzene of fuel distributors are considerably below the limit values set by the Italian legislation. The most frequently used biological exposure indicator was trans, trans-muconic urinary acid (TTMA-U). In order to reduce as much as possible the health risks for refuelers, it is needed that employers, workers and occupational physicians pay more attention to their respective duties, ensuring corrective or ameliorative interventions focused on assessment of the risk of carcinogens, supply and use of PPE, design of workplaces, health surveillance and biological monitoring of workers. The poor value of the end-of-shift TTMA-U as a biological indicator of exposure to low-dose benzene is also confirmed.

Assessment of liver and renal function tests among gasoline exposed gas station workers in Mekelle city, Tigray region, Northern Ethiopia.

BACKGROUND: Volatile organic compounds such as gasoline and other fuels are associated with a wide variety of deleterious health effects including liver and kidney diseases. Gasoline station workers are exposed to a mixture of hydrocarbons during dispensing. However, no published studies investigated the liver and renal function tests of gasoline station workers in Ethiopia. Therefore the aim of this study was to assess liver and renal function tests among gasoline station workers. METHOD: A comparative cross sectional study was conduct from January 2018 to April 2018 at Mekelle city, Tigray region, Northern Ethiopia. Liver and renal function tests were analyzed on gasoline exposed (n = 43) and controls (n = 47) by Pentra C400 automated clinical chemistry analyzer. Student independent t-test and one way-ANOVA statistical methods were employed using SPSS Ver23. P-value < 0.05 was regarded as statistically significant. RESULT: The mean level of ALT, AST, Urea, creatinine, and uric acid was significantly higher among gasoline stations workers when compared to control study participants. There was also a significant increase in ALT, AST, Urea, creatinine and uric acid among gasoline stations with above 6 years exposure when compared with those exposed for ≤2 and3-6years. CONCLUSION: These findings suggest that increasing liver and renal parameters may be associated with exposure to gasoline and it is dependent on time of exposure to gasoline.

Effects of Occupational Hazards on Job Stress and Mental Health of Factory Workers and Miners: A Propensity Score Analysis.

This study is to evaluate the effects of different occupational hazards on job stress and mental health of factory workers and miners. A total of 6120 workers from factories and mining enterprises in seven districts and one district of Urumqi were determined using the stratified cluster random sampling method. The Effort-Reward Imbalance (ERI) questionnaire and the Symptom Checklist-90 (SCL-90) were used to evaluate the effects of occupational hazard factors on job stress and mental health of workers. The propensity score analysis was used to control the confounding factors. The occupational hazards affecting job stress of workers were asbestos dust (OR = 1.3, 95% CI: 1.09-1.55), benzene (OR = 1.25, 95% CI: 1.10-1.41), and noise (OR = 1.39, 95% CI: 1.22-1.59). The occupational hazards affecting the mental health of workers were coal dust (OR = 1.19, 95% CI: 1.02-1.38), asbestos dust (OR = 1.58, 95% CI: 1.32-1.92), benzene (OR = 1.28, 95% CI: 1.13-1.47), and noise (OR = 1.23, 95% CI: 1.07-1.42). Different occupational hazards have certain influence on job stress and mental health of factory workers and miners. The enhancements in occupational hazard and risk assessment, occupational health examination, and occupational protection should be taken to relieve job stress and enhance the mental health of factory workers and miners.

"Absurd" Contract Dodge Rejected: Court Lets Cancer Center's Debt-Collection Suit Proceed.

Appeals court denies "free speech" challenge to cancer center's debt-collection suit.

[Investigation on the health status of workers exposed to benzene in one province].

Objective: To explore the health status of occupational benzene exposure workers, and to provide a scientific basis for the development of reasonable health monitoring and effective protective measures. Methods: In March 2019, the occupational health surveillance data were collected including blood pressure, electrocardiogram, blood routine, urine routine, liver function, etc of 7810 benzene contact workers in 150 enterprises in Jiangxi Province in 2017, to analyze and assess their health status. Results: Among the 7810 benzene workers, there were 5451 males and 2359 females; the average age was (40.5±9.9) years; and the median benzene working age was 3.5 years. The detection rate of hypertension was 17.0% (734/4317) , the abnormal rate of urine routine was 15.7% (1227/7810) , the abnormal rate of liver function was 8.6% (356/4147) , and the abnormal rate of electrocardiogram was 12.3%(963/7810). The detection rates of low count number of leukocytes, platelets, neutrophils and occupational contraindications were 4.6%(360/7810) , 1.4%(108/7810) , 4.2%(330/7810) and 1.4%(110/7810) , respectively. The detection rates of low count number of leukocytes, platelets and neutrophils in female were all higher than those in male (P<0.05). The detection rates of low count number of platelets, neutropenia and occupational contraindications increased with age and working age (P<0.05 ). There were significant differences in the detection rates of low count number of leukocytes, platelets, neutrophils and occupational contraindications among benzene workers in different economic types (P<0.05) , and the highest among foreign companies, followed by private enterprise. There were statistically significant differences in the detection rates of low count number of platelets, neutrophils and occupational contraindications in benzene workers of different enterprise sizes (P<0.05) , and the highest was found in micro enterprises, followed by small enterprises. Conclusion: In 2017, the occupational health status of workers exposed to benzene in Jiangxi province is not optimistic. It is necessary to strengthen the occupational health supervision of small and micro-sized enterprises, foreign enterprises and private enterprises, take the initiative to improve health surveillance, and effectively protect the physical and mental health of workers.

Residential exposure to petrochemical industrial complexes and the risk of leukemia: A systematic review and exposure-response meta-analysis.

Exposure to chemicals produced by petrochemical industrial complexes (PICs), such as benzene, ionizing radiation, and particulate matters, may contribute to the development of leukemia. However, epidemiological studies showed controversial results. This systematic review and meta-analysis aimed to summarize the association between residential exposure to PICs and the risk of leukemia incidence, focusing on exposure-response effects. We searched PubMed, Embase, Web of Science, and Cochrane Library databases for studies published before September 1st, 2019. Observational studies investigating residential exposure to PICs and the risk of leukemia were included. The outcome of interest was the incidence of leukemia comparing to reference groups. Relative risk (RR) was used as the summary effect measure, synthesized by characteristics of populations, distance to PICs, and calendar time in meta-regression. We identified 7 observational studies, including 2322 leukemia cases and substantial reference groups, in this meta-analysis. Residential exposure to PICs within a maximal 8-km distance had a 36% increased risk of leukemia (pooled RR = 1.36, 95% CI = 1.14-1.62) compared to controls, regardless of sex and age. In terms of leukemia subtypes, residential exposure to PICs was associated with the risks of acute myeloid leukemia (AML, pooled RR = 1.61, 95% CI = 1.12-2.31) and chronic lymphocytic leukemia (CLL, pooled RR = 1.85, 95% CI = 1.11-6.42). In meta-regression, the positive association occurred after 10 years of follow-up with a pooled RRs of 1.21 (95% CI = 1.02-1.44) and then slightly increased to 1.77 (95% CI = 1.35-2.33) at 30 years after follow-up. No effect modification was found by sex, age, and geographic locations.

Up-regulation of DNMT3b contributes to HOTAIRM1 silencing via DNA hypermethylation in cells transformed by long-term exposure to hydroquinone and workers exposed to benzene.

Benzene exposure is a risk factor of acute myeloid leukemia (AML), during such carcinogenesis long non-coding RNAs (lncRNAs) are important epigenetic regulators. HOTAIRM1 (HOXA transcript antisense RNA, myeloid-specific 1) plays an indispensable role in the development of AML. Hydroquinone (HQ) is one major metabolite of benzene and its ideal replacement in toxicology research. But the influence of benzene or HQ on HOTAIRM1 expression in AML associated pathway is still unclear. In the TK6 cells with short-term exposure to HQ (HQ-ST cells) or long term HQ exposure induced malignant transformed TK6 cells (HQ-MT cells), the relationship between DNMT3b and HOTAIRM1 was explored. Comparing to counterparts, HOTAIRM1 expression was increased firstly and then decreased in HQ-ST cells, and definitely decreased in HQ-MT cells; while the expression change tendency of DNMT3b was in contrast to that of HOTAIRM1. Moreover, the average HOTAIRM1 expression of 17 paired workers being exposed to benzene within 1.5 years was increased, but that of the remaining 92 paired workers with longer exposure time was decreased. Furthermore, in 5-AzaC (DNA methyltransferase inhibitor) or TSA (histone deacetylation inhibitor) treated HQ-MT cells, the expression of HOTAIRM1 was restored by reduced DNA promoter methylation levels. HQ-MT cells with DNMT3b knockout by CRISPR/Cas9 displayed the promoter hypomethylation and the increase of HOTAIRM1, also confirmed in benzene exposure workers. These suggest that long term exposure to HQ or benzene might induce the increase of DNMT3b expression and the promoter hypermethylation to silence the expression of HOTAIRM1, a possible tumor-suppressor in the AML associated carcinogenesis pathway.

Maternal exposure to benzene and toluene and preterm birth. A longitudinal study

ABSTRACT BACKGROUND: Exposure to air pollutants has several effects on human health, including during pregnancy. OBJECTIVE: To identify whether exposure to benzene and toluene among pregnant women contributes to preterm delivery. DESIGN AND SETTING: Longitudinal study using data on newborns from mothers living in São José dos Campos (SP) in 2016, who had been exposed to benzene and toluene. METHODS: A logistic regression model with three hierarchical levels was constructed using maternal variables relating to newborns, and using benzene and toluene concentrations in quartiles. Occurrences of cesarean births, twins or malformations were excluded. Maternal exposure windows of 5, 10, 15, 30, 60 and 90 days prior to delivery were considered. RESULTS: Out of the 9,562 live births, 3,671 newborns were included and 343 newborns were born at less than 37 weeks of gestation (9.3%). The average birth weight was 3,167.2 g. Exposure to benzene and toluene was significantly associated (P = 0.04) with preterm delivery in the five-day window. There was no association in any of the other exposure windows. CONCLUSIONS: It was possible to identify that maternal exposure to benzene and toluene has an acute effect on preterm delivery.