Multiple air pollutant exposure and lung cancer in Tehran, Iran.

Lung cancer is the most rapidly increasing malignancy worldwide with an estimated 2.1 million cancer cases in the latest, 2018 World Health Organization (WHO) report. The objective of this study was to investigate the association of air pollution and lung cancer, in Tehran, Iran. Residential area information of the latest registered lung cancer cases that were diagnosed between 2014 and 2016 (N = 1,850) were inquired from the population-based cancer registry of Tehran. Long-term average exposure to PM10, SO2, NO, NO2, NOX, benzene, toluene, ethylbenzene, m-xylene, p-xylene, o-xylene (BTEX), and BTEX in 22 districts of Tehran were estimated using land use regression models. Latent profile analysis (LPA) was used to generate multi-pollutant exposure profiles. Negative binomial regression analysis was used to examine the association between air pollutants and lung cancer incidence. The districts with higher concentrations for all pollutants were mostly in downtown and around the railway station. Districts with a higher concentration for NOx (IRR = 1.05, for each 10 unit increase in air pollutant), benzene (IRR = 3.86), toluene (IRR = 1.50), ethylbenzene (IRR = 5.16), p-xylene (IRR = 9.41), o-xylene (IRR = 7.93), m-xylene (IRR = 2.63) and TBTEX (IRR = 1.21) were significantly associated with higher lung cancer incidence. Districts with a higher multiple air-pollution profile were also associated with more lung cancer incidence (IRR = 1.01). Our study shows a positive association between air pollution and lung cancer incidence. This association was stronger for, respectively, p-xylene, o-xylene, ethylbenzene, benzene, m-xylene and toluene.

Aberrant lncRNA Profiles Are Associated With Chronic Benzene Poisoning and Acute Myelocytic Leukemia.

OBJECTIVE: This study investigates the mechanisms of benzene hematotoxicity. METHODS: We used microarray to detect expression profiles of long non-coding RNAs (lncRNAs) and mRNAs in peripheral lymphocytes from chronic benzene poisoning, acute myelocytic leukemia, and healthy controls. The lncRNAs and mRNAs were validated using real-time quantitative PCR (RT-qPCR). Cytokinesis-block micronucleus assay was used to analyze chromosomal aberration. RESULTS: We found 173 upregulated and 258 downregulated lncRNAs, and 695 upregulated and 804 downregulated mRNAs. The lncRNA CUST_40243 and mRNA PDGFC and CDKN1A associated with chronic benzene poisoning. Relevant inflammatory response, hematopoietic cell lineage, and cell cycle may be important pathways for the sifted lncRNAs and mRNAs. Furthermore, micronuclei frequency was significantly higher in off-post chronic benzene poisoning patients. CONCLUSIONS: Chromosomal aberration induced by benzene exposure is irreversible. The lncRNA CUST_40243 and mRNA PDGFC and CDKN1A are related to chronic benzene poisoning.

[To discuss the problems existing in the labor ability appraisal of an occupational chronic benzene poisoning incidence].

Three female workers in a golf club production company in Guangzhou were diagnosed with occupational chronic mild benzene poisoning. Two of the female workers were assessed as Grade 7 disabilities. One female worker showed the symptoms of the decline of whole blood cells for unknown reasons in the later stages of the medical period. The final assessment was a Class 5 disability. The problems in this work ability appraisal include: the injury condition of the patient who has not been stable during the work ability appraisal, and the contradiction between the disability grade and the occupational disease diagnosis conclusion. In order to avoid similar situations, the following recommendations are recommended: after the worker's injury situation is relatively stable, the assessment will be conducted, the employer will actively exercise the right to review and appraisal, and the diagnosis of occupational diseases will be included in the evaluation criteria for disability grade.

Niveles urinarios de ácido trans, trans mucónico y orto cresol en una población infanto-juvenil residente en Ciudad Autónoma de Buenos Aires y Conurbano Bonaerense / Urinary levels of trans, trans muconic and ortho cresol in an infant-juvenile population resident in the Autonomous City of Buenos Aires and the Conurbano of Buenos Aires

Introducción: la exposición crónica al benceno y tolueno produce alteraciones sobre la médula ósea y el sistema nervioso central, entre otros. En orina, el ácido trans, trans mucónico (t, t-MA) es uno de los biomarcadores de exposición al benceno y el o-cresol (oCre) al tolueno. Objetivo: analizar los resultados de los niveles de t, t-MA y oCre urinarios en una población infanto-juvenil residente en Ciudad Autónoma de Buenos Aires y Conurbano Bonaerense potencialmente expuesta a benceno y tolueno ambiental. Materiales y métodos: se realizó un estudio retrospectivo de los resultados de t, t-MA y oCre urinarios. Las muestras de orina ingresaron al laboratorio con solicitud de t, t-MA (n=1519) y oCre (n=1447) durante el período 2011-2017 (rango etario entre 0 a 19 años). El t, t-MA se cuantificó por UFLC con detector de arreglo de diodos y el oCre por CG con detector de ionización por llama. Resultados: la edad promedio de los pacientes fue de 4,8 años y la mediana 4,6 años.Las concentraciones de t, t-MA urinario fueron: menor de 50 μg/l (44,8%); entre 50-500 μg/l (52,1%) y mayores de 500 μg/l (3,1%). Expresadas por gramo de creatinina: entre 15-163 μg/g creatinina (60,4%) y mayores de 163 μg/g creatinina (39,6%). El límite de cuantificación de t, t-MA fue de 50 μg/l. Las concentraciones de oCre urinario fueron: menor de 0,20 mg/l (97,7%) y entre 0,20-0,50 mg/l (2,3%) y mayor de 0,50 mg/l (0%). Expresadas por gramo de creatinina: menor de 0,30 mg/g creatinina en el 0,8% y mayores de 0,30 mg/g creatinina en el 1,5%. El límite de cuantificación de oCre fue de 0,20 mg/l. Conclusiones: los resultados del trabajo podrían indicar una contaminación ambiental persistente, en especial en el Conurbano Bonaerense, donde debería continuarse el monitoreo de algunas zonas. Pero, por otro lado, es de vital importancia tener en cuenta los factores de confusión, tales como la dieta, la exposición al humo de tabaco ambiental (fumador pasivo) y la tasa de excreción renal que llevarían a una sobre-estimación de los resultados y a una incorrecta toma de decisiones.

Introduction: Chronic exposure to benzene and toluene produces alterations in the bone marrow and the central nervous system, among other effects. In urine, trans, trans muconic acid (t, t-MA) is one of the biomarkers of exposure to benzene and o-cresol (oCre), to toluene. Objective: To analyze the results of urinary t, t-MA and oCre levels in an infant-juvenile population resident in the Autonomous City of Buenos Aires and the Conurbano Bonaerense, potentially exposed to environmental benzene and toluene. Materials and methods: A retrospective study of urinary t, t-MA and oCre results was performed. The urine samples entered the laboratory with the request of t, t-MA (n = 1519) and oCre (n = 1447) during the period 2011- 2017. The age range of the population was between 0 and 19 years. The t, t-MA was quantified by UFLC with diode array detector and the oCre by GC with flame ionization detector. Results: The average age of the patients was 4.8 years and the median age was 4.6 years. The urinary concentrations of t, t-MA were: below 50 μg/l (44.8%); between 50-500 μg/l (52.1%) and above 500 μg/l (3.1%). Expressed per gram of creatinine: between 15-163 μg/g creatinine (60.4%) and greater 163 μg/g creatinine (39.6%). The limit of quantification of t, t-MA was 50 μg/l. The urinary oCre concentrations were: less than 0.20 mg/l (97.7%) and between 0.20-0.50 mg/l (2.3%). Expressed per gram of creatinine: less than 0.30 mg/g creatinine in 0.8% and greater than 0.30 mg/g creatinine in 1.5%. The limit of quantification of oCre was 0.20mg/l. Conclusions: The results of the study could indicate persistent environmental contamination, especially in the Conurbano Bonaerense, where monitoring of some areas should be continued. However, it is of vital importance to take into account the confounding factors, such as diet, exposure to environmental tobacco smoke (passive smoking) and the rate of renal excretion, which would lead to an over-estimation of the results and to incorrect decision-making.

Aberrant DNA Methylation of Two Tumor Suppressor Genes, p14ARF and p15INK4b, after Chronic Occupational Exposure to Low Level of Benzene.

BACKGROUND: Exposure to benzene would be associated with many diseases including leukemia. Epigenetic alterations seem to be among the main mechanisms involved. OBJECTIVE: To determine if chronic occupational exposure to low level of benzene would be associated with DNA methylation. METHODS: Global DNA methylation and promoter-specific methylation of the two tumor suppressor genes, p14ARF and p15INK4b, were assessed employing methylation-specific PCR using the DNA extracted from 40 petrochemical workers exposed to ambient benzene levels of <1 ppm, and 31 office workers not exposed to benzene or its derivatives. RESULTS: While an increase in global DNA methylation of 5% in p14ARF (p=0.501) and 28% in p15INK4b (p=0.02) genes was observed in the exposed group, no hypermethylation in either of the studied genes was observed in the unexposed group. No significant association was found between the frequency of aberrant methylation and either of age, work experience, and smoking habit in the exposed group. CONCLUSION: Chronic occupational exposure to lower than the permissible exposure limit of benzene may still result in DNA methylation of tumor suppressor genes that may ultimately lead to development of cancer.

Proteome analysis of the potential serum biomarkers for chronic benzene poisoning.

The aim of our study is to seek novel specific biomarkers which could provide clues to the mechanism of chronic benzene poisoning (CBP) and might also be used as specific markers for early detection and diagnosis. In this study, a comparative serological proteome analysis between normal controls and CBP patients at three different levels of poisoning were performed via a 2D-DIGE and MALDI-TOF-MS. As the result a total of 10 proteins were found significantly altered between the normal and the mild, moderate and severe poisoning. The identified differentially expressed proteins were classified according to their molecular functions, biological processes, and protein classes, and three important serum proteins among them, apolipoproteinA-1, alpha-1-antitrypsin and complement C3, were further confirmed by immune turbidimetric analysis for their significant up-regulation in the CBP patients. Our findings suggest that these differential proteins may help elucidate the mechanism of CBP and provide potential biomarkers for diagnosis.

The protective effect of diallyl trisulfide on cytopenia induced by benzene through modulating benzene metabolism.

It has been known that metabolism of benzene is necessary for its toxicity. The purpose of our study is to investigate the effect of diallyl trisulfide (DATS) on attenuating cytopenia in peripheral blood introduced by benzene through regulating benzene metabolism in rats. We established benzene poisoning model with benzene (1.3 g/kg), while the DATS treatment groups were treated with DATS plus benzene (15 or 30 mg/kg) for 28 days, respectively. The results of blood parameters and concentration of metabolites of benzene (t, t-MA and SPMA) determination in urine showed that DATS could effectively attenuate the cytopenia induced by benzene through regulating benzene metabolism. Western blot and chemical method were used to detect the activities and protein expression levels of enzymes CYP2E1 and GSTT1 in liver and enzymes MPO and NQO1 in bone marrow were tested. The results suggested that the inhibition of bioactivation in liver and bone marrow catalyzed by CYP2E1 and MPO and the activation of detoxification catalyzed by GSTT1 and NQO1 might be the critical mechanism, through which DATS modulated benzene metabolism to prevent benzene-induced cytopenia.

Critique of the IARC 100F Working Group Evaluation of Occupational Benzene Exposure: Suggestions for the October 2017 Benzene-Only Working Group Meeting.

Health agencies and institutions utilize International Agency for Research on Cancer (IARC) monographs because they are said to represent authoritative cancer evaluations and scientific references. The United States National Cancer Institute has provided support for the IARC Monographs Program for more than three decades. The Volume 100F Monograph, which was published in 2012, reports the evaluations of benzene and more than two dozen other agents performed by the IARC Working Group (WG) that met in Lyon, France from 20 to 27 October 2009. All had already been judged to be human carcinogens. This commentary discusses errors in the occupational exposure section (1.1.3) of the 100F Benzene Monograph ("monograph"). Millions of workers in developed and developing countries have long been known to be routinely exposed to benzene. Since exposures may exceed occupational exposure limits, the hope is that this commentary will be considered by the IARC benzene-only WG at its meeting in October 2017.

Adverse Health Complaints of Adults Exposed to Benzene After a Flaring Disaster at the BP Refinery Facility in Texas City, Texas.

OBJECTIVE: The objective of this study was to assess the adverse health symptoms experienced by adult subjects who were exposed to benzene after a flaring disaster at the BP refinery in Texas City, Texas. METHODS: A total of 2162 adults aged 18 years or older and exposed to benzene were included. Using the patients' medical charts, we collected and analyzed data on health complaints as well as the patients' serum levels of beta-2-microglobulin and urinary excretion of phenol. RESULTS: A total of 11,368 health symptom complaints were reported in 2162 adults exposed to benzene. Neurological symptoms occurred most frequently (174%), followed upper respiratory symptoms (115%), cough (31%), painful joints (30%), cardiac symptoms (28%), dermatological symptoms (28%), gastrointestinal symptoms (27%), diarrhea (25%), vision symptoms (21%), and nausea/vomiting (19%). Logistic regression analysis indicated that urinary symptoms (R2=0.65) and painful joints (R2=0.44) were positively associated with increasing age in benzene-exposed subjects. CONCLUSION: Adult subjects exposed to benzene experience a range of adverse health symptoms and an altered profile of urinary phenol, thus indicating they are at high risk of developing serious future health complications. (Disaster Med Public Health Preparedness. 2018;12:232-240).

Down-regulation of miRNA-451a and miRNA-486-5p involved in benzene-induced inhibition on erythroid cell differentiation in vitro and in vivo.

Exposure to high-dose benzene leads to the inhibition of erythroid differentiation. However, whether lower doses of benzene exposure resemble high-dose effects in erythroid differentiation, as well as the underlying mechanisms, remains largely unknown. To identify the microRNAs (miRNAs) specifically responsible for benzene exposure and their regulatory role in erythroid differentiation, we performed miRNA microarray in CD34+ hematopoietic progenitor cells isolated from human umbilical cord blood after treatment with hydroquinone (HQ), a metabolite of benzene at concentrations of 0, 1.0, 2.5, and 5.0 µM. As a result, HQ treatment inhibited erythroid differentiation in a dose-response manner. miRNA microarray analysis revealed that miRNA-451a, miRNA-486-5p and miRNA-126-3p expression were significantly lower in HQ-treated CD34+ hematopoietic progenitor cells. In vitro studies showed that miRNA-451a and miRNA-486-5p were up-regulated during erythroid differentiation both in CD34+ hematopoietic progenitor cells and K562 cells. The increase in the percentage of benzidine-positive cells and the expression of γ-globin in K562 cells transfected with either miRNA-451a or miRNA-486-5p mimic indicated that both miRNAs played a role in the promotion of erythroid cell differentiation. Overexpression of either miRNA-451a or miRNA-486-5p attenuated the inhibitory effects on erythroid differentiation in HQ-treated K562 cells. In vivo study showed a decreasing count of peripheral red blood cell (RBC) in C57BL/6J male mice treated with aerosol benzene at concentrations of 0, 1, 5, 25 ppm (time weight average, TWA). In addition, the expression of miRNA-451a or miRNA-486-5p was negatively correlated with the concentration of benzene inhalation on erythroid toxicity of C57BL/6J mice. Particularly, the decline in miRNA-451a and miRNA-486-5p expression appeared in male chronic benzene poisoning patients, and was correlated with a constant decrease in their RBC counts over the first 3 months after being diagnosed. These findings indicate that the suppression of miRNA-451a or miRNA-486-5p might be associated with the benzene-induced perturbation of erythroid cell differentiation.

Genotoxic effects of occupational exposure to benzene in gasoline station workers.

Benzene, a hazardous component of gasoline, is a genotoxic class I human carcinogen. This study evaluated the genotoxic effects of occupational exposure to benzene in gasoline stations. Genotoxicity of exposure to benzene was assessed in peripheral blood leucocytes of 62 gasoline station workers and compared with an equal numbers of matched controls using total genomic DNA fragmentation, micronucleus test and cell viability test. An ambient air samples were collected and analyzed for Monitoring of benzene, toluene, ethyl benzene and xylene (BTEX) in work environment and control areas. DNA fragmentation, micronucleus and dead cells percent were significantly higher in exposed workers than controls. Level of benzene, Toluene, Ethyl benzene and xylene in the work environment were higher than the control areas and the permissible limits. Gasoline station workers occupationally exposed to benzene are susceptible to genotoxic effects indicated by increased DNA fragmentation, higher frequency of micronucleus and decreased leukocytes viability.

Benzene exposure from the BP refinery flaring incident alters hematological and hepatic functions among smoking subjects.

OBJECTIVES: To evaluate the health effects of benzene exposure among smoking subjects from a prolonged flaring incident that occurred at the British Petroleum (BP) refinery in Texas City, USA. MATERIAL AND METHODS: The study included smoking subjects who had been exposed and unexposed to the benzene release. Using medical charts, clinical data including white blood cell (WBC) counts, platelet counts, hemoglobin, hematocrit, blood urea nitrogen (BUN), creatinine, alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) in the case of smoking subjects exposed to benzene was reviewed and analyzed. RESULTS: A total of 791 tobacco smoking subjects (benzene-exposed: N = 733, unexposed: N = 58) were included. Benzene-exposed subjects had significantly higher levels of WBC (×103/µl) counts (8±2.1 vs. 7.5±1.6, p = 0.003) and platelet (×103/µl) counts (263.7±69.7 vs. 222.9±44.3, p = 0.000) as compared with the unexposed subjects. The mean hemoglobin, hematocrit, BUN, and creatinine levels did not differ significantly between the benzene-exposed and -unexposed smoking subjects. Serum levels of ALP (IU/l) was significantly elevated in the benzene-exposed subjects compared with the unexposed subjects (84.5±16.9 vs. 73.8±15.9, p = 0.002). Similarly, benzene-exposed subjects had significantly higher levels of AST and ALT as compared with those unexposed subjects. CONCLUSIONS: Despite a smoking history, residents exposed to benzene from the prolonged BP flaring incident experienced significant alterations in hematological and hepatic functions indicating their vulnerability to the risk of developing hepatic or blood related disorders. Int J Occup Med Environ Health 2017;30(6):849-860.

[A study on the effects of exposure to benzene on the activity of immunoglobulin E].

Objective: To analyze the level of immunoglobulin E (IgE) changes with benzene exposure workers. Methods: Firstly, through occupational health monitoring, 68 hospitalized cases were discovered who were suspected chronic benzene poisoning. Secondly, according to the GBZ68-2013《The diagnosis of occupational benzene poisoning》standard diagnosis and indexing, 68 cases were divided into the benzene poisoning group (n= 29) and the benzene exposure group (n=39) . 50 cases of healthy workers without benzene exposure were for the control group. Use the immune luminescence method to detect IgE levels. Thirdly, Case-control study was used, observing IgE changes though the three groups by statistical analysis. Results: Compared with control group, the level of leukocyte、neutrophil and IgE was drop in benzene exposure group with statistically significant (P<0.05) . Compared with benzene exposure group, IgE of benzene poisoning group was rise, with statistically significant (P<0.05) , IgE of mild benzene poisoning group rise the most obvious, with statistically significant (P<0.05) . Compared with benzene exposure group, IgE of moderate benzene poisoning group was drop, without statistically significant (P>0.05) . Conclusion: Benzene occupational exposure can induce immunosuppression, IgE decreases, and reduces immune surveillance. The response of the IgE level in the mild benzene poisoning patients was significantly elevated, whether it is protective response of the body immune function needs to be studied further investigated.

Benzene and its metabolite decreases cell proliferation via LncRNA-OBFC2A-mediated anti-proliferation effect involving NOTCH1 and KLF15.

LncRNA has been considered to play a crucial role in the progression of several diseases by affecting cell proliferation. However, its role in benzene toxicity remains unclear. Our study showed that the expression of lncRNA-OBFC2A increased accompanied with the change of cell proliferation related-genes in benzene-exposed workers. In vitro experiments, 1,4-Benzoquinone dose-dependently inhibited cell proliferation and simultaneously caused the decrease of NOTCH1 expression and the increase of KLF15 in AHH-1 cell lines. Meanwhile, 1, 4-Benzoquinone obviously increased the expression of lncRNA-OBFC2A, which was consistent with our previous population results. Therefore, we propose that lncRNA-OBFC2A is involved in benzene toxicity by regulating cell proliferation. Further, we successfully constructed a lentivirus model of interfering the expression of lncRNA-OBFC2A. After interfering lncRNA-OBFC2A, the cell proliferation inhibition and the expression of NOTCH1 and KLF15 induced by 1, 4-Benzoquinone were reversed. Subsequently, RNA fluorescence in situ Hybridization assay showed that lncRNA-OBFC2A was located in cell nuclei. These results suggest that benzene and its metabolite decreases cell proliferation via LncRNA-OBFC2A-mediated anti-proliferation effect involving NOTCH1 and KLF15. LncRNA-OBFC2A can be a potential biomarker for benzene toxicity.

Benzene poisoning, clinical and blood abnormalities in two Brazilian female gas station attendants: two case reports.

BACKGROUND: Brazilian gas station workers are chronically exposed to benzene, toluene, xylene (BTX) during their working time. Describe below two cases of latin female gas station workers with benzene poisoning symptoms and miscarriage history. CASE PRESENTATION: In both cases were identified complex chromosomal rearrangements (CCR) with fluorescence in situ hybridization, applied to whole chromosome paints by chromosomes 1, 2 and 4. The lower natural killer cell (NK) cells have also been observed in cases correspondents, especially the rare type of NK (NKbright) in their peripheral blood cells. CONCLUSIONS: It is known that acquired chromosomal aberrations are positively correlated with cancer and reproductive risk. In concordance, lower NK cytotoxicity increases the risk for cancer, as well. Thus, this is the first study providing hints on a possible causative relation of lower NK cytotoxicity and increase rates of chromosomal rearrangements including CCRs.

Illness Symptoms Experienced by Children Exposed to Benzene After a Flaring Incident at the BP Refinery Facility in Texas City.

Objective To evaluate the illness symptoms experienced by children who were exposed to benzene following a flaring incident at the BP refinery in Texas City, Texas. Methods A total of 641 children, aged <17 years, exposed to benzene were included. Using medical charts, data on the children's illness symptoms as well as the serum levels of ß-2-microglobulin and the amount of urinary excretion of phenol were reviewed and analyzed. Results A total of 1790 illness symptoms were reported in 641 children exposed to benzene. Upper respiratory symptoms were the most (67%) frequently reported, followed by neurological symptoms (57%), diarrhea (25%), and cough (24%). Logistic regression analysis indicated that neurological symptoms (R(2) = 0.75), chest pain (R(2) = 0.64), joint pain (R(2) = 0.57), and vision difficulty (R(2) = 0.54) were positively associated with increasing age. ß-2-Microglobulin levels were significantly higher in children <5 years compared with those >5 year (P = .04). Conversely, urinary phenol levels were significantly lower in children <5 years compared with those >5 years (P = .00). Conclusion Together, these findings reveal that children exposed to benzene experience a range of illness symptoms and an altered profile of urinary phenol indicating their vulnerability to potentially increased health complications.

[Histone acetylation modification of topoisomerase enzyme â ¡α promoter regulation factors in patients with chronic benzene poisoning].

OBJECTIVE: To investigate histone acetylation modification of topoisomerase enzyme Ⅱα (TOPOⅡα) promoter regulation factors in patients with chronic benzene poisoning, to explore the possible regulatory mechanism of TOPOⅡα involved in toxicity of chronic benzene poisoning; METHODS: The bone marrow samples were from 25 chronic benzene poisoning cases and 25 controls. The Chromatin Immunoprecipitation (ChIP) assay was carried out to study the possible mechanism of TOPOⅡα promoter regulation factors expression changes. TOPOⅡα promoter regulation factors mRNA were detected by RT-PCR technique. RESULTS: (1) Compared with the control, the histone H4 acetylation, histone H3 acetylation level of TOPOⅡα promoter regulation factors SP1, ATF-2, SP3, NF-YA, P53, C-MYB, ICBP90, NF-M in chronic benzene poisoning patients decreased, with the significant difference (P<0.05) , except for C-JUN (P>0.05) ; (2) The mRNA expression of TOPOⅡαpromoter regulation factors SP1, NF-YA, C-MYB, C-JUN and NF-M were significantly lower than in the control with the significant difference (P<0.05) , while the expression of SP3、P53 mRNA increased (P<0.05) , ATF-2、ICBP90 mRNA wasn't changed (P>0.05) . CONCLUSION: (1) Chronic benzene poisoning TOPO Ⅱα promoter regulation factors histone modification changes accompanied with mRNA level changed. (2) Histone acetylation modification of topoisomerase enzyme Ⅱα promoter regulation factors takes important role in the benezen's Hematopoietic toxicity.

Detrimental Health Effects of Benzene Exposure in Adults After a Flaring Disaster at the BP Refinery Plant in Texas City.

OBJECTIVE: To examine the adverse effects of benzene exposure in adults from a prolonged flaring disaster at the BP refinery in Texas City, Texas. METHODS: Adults aged 18 years and older who had been exposed and unexposed to benzene were included. We reviewed medical charts and compared measures of white blood cells (WBCs), platelets, hemoglobin, hematocrit, blood urea nitrogen (BUN), creatinine, alkaline phosphatase (ALP), aspartate amino transferase (AST), and alanine amino transferase (ALT) in exposed and unexposed adults. RESULTS: Records from 2213 adults (benzene exposed, n=1826; unexposed, n=387) were reviewed. Benzene-exposed subjects had significantly higher WBC counts (7.9±2.3 vs 6.8±1.6×10(3) per µL, P=0.0000) and platelet counts (270.8±60.9 vs 242.5±53.7×10(3) per µL, P=0.0000) than did the unexposed subjects. Serum creatinine levels were also significantly higher in the exposed group than in the unexposed group (1.0±0.2 vs 0.8±0.2 mg/dL, P=0.000). Serum levels of ALP were significantly higher in the exposed subjects than in the unexposed subjects (82.1±15.6 vs 71.8±8.2 IU/L, P=0.000). Similarly, benzene-exposed subjects had significantly higher levels of AST (26.2±6.4 vs 19.7±5.3 IU/L, P=0.000) and ALT (30.6±10.8 vs 20.9±9.6 IU/L, P=0.000) than in those unexposed to benzene. CONCLUSION: Benzene exposure resulted in significant alterations in hematologic and liver profiles in adults.

Genetic Polymorphisms in XRCC1, CD3EAP, PPP1R13L, XPB, XPC, and XPF and the Risk of Chronic Benzene Poisoning in a Chinese Occupational Population.

OBJECTIVES: Individual variations in the capacity of DNA repair machinery to relieve benzene-induced DNA damage may be the key to developing chronic benzene poisoning (CBP), an increasingly prevalent occupational disease in China. ERCC1 (Excision repair cross complementation group 1) is located on chromosome 19q13.2-3 and participates in the crucial steps of Nucleotide Excision Repair (NER); moreover, we determined that one of its polymorphisms, ERCC1 rs11615, is a biomarker for CBP susceptibility in our previous report. Our aim is to further explore the deeper association between some genetic variations related to ERCC1 polymorphisms and CBP risk. METHODS: Nine single nucleotide polymorphisms (SNPs) of XRCC1 (X-ray repair cross-complementing 1), CD3EAP (CD3e molecule, epsilon associated protein), PPP1R13L (protein phosphatase 1, regulatory subunit 13 like), XPB (Xeroderma pigmentosum group B), XPC (Xeroderma pigmentosum group C) and XPF (Xeroderma pigmentosum group F) were genotyped by the Snapshot and TaqMan-MGB® probe techniques, in a study involving 102 CBP patients and 204 controls. The potential interactions between these SNPs and lifestyle factors, such as smoking and drinking, were assessed using a stratified analysis. RESULTS: An XRCC1 allele, rs25487, was related to a higher risk of CBP (P<0.001) even after stratifying for potential confounders. Carriers of the TT genotype of XRCC1 rs1799782 who were alcohol drinkers (OR = 8.000; 95% CI: 1.316-48.645; P = 0.022), male (OR = 9.333; 95% CI: 1.593-54.672; P = 0.019), and had an exposure of ≤12 years (OR = 2.612; 95% CI: 1.048-6.510; P = 0.035) had an increased risk of CBP. However, the T allele in PPP1R13L rs1005165 (P<0.05) and the GA allele in CD3EAP rs967591 (OR = 0.162; 95% CI: 0039~0.666; P = 0.037) decreased the risk of CBP in men. The haplotype analysis of XRCC1 indicated that XRCC1 rs25487A, rs25489G and rs1799782T (OR = 15.469; 95% CI: 5.536-43.225; P<0.001) were associated with a high risk of CBP. CONCLUSIONS: The findings showed that the rs25487 and rs1799782 polymorphisms of XRCC1 may contribute to an individual's susceptibility to CBP and may be used as valid biomarkers. Overall, the genes on chromosome 19q13.2-3 may have a special significance in the development of CBP in occupationally exposed Chinese populations.