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1.
Arch Toxicol ; 98(2): 365-374, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38142431

RESUMO

Several recent reports indicate health hazards for workers with below occupational limit exposure to benzene (BZ). Our updated review indicates that such low exposures induced traditional as well as novel toxicity/genotoxicity, e.g., increased mitochondria copy numbers, prolongation of telomeres, impairment of DNA damage repair response (DDRR), perturbations of expression in non-coding RNAs, and epigenetic changes. These abnormalities were associated with alterations of gene expression and cellular signaling pathways which affected hematopoietic cell development, expression of apoptosis, autophagy, etc. The overarching mechanisms for induction of health risk are impaired DDRR, inhibition of tumor suppressor genes, and changes of MDM2-p53 axis activities that contribute to perturbed control for cancer pathways. Evaluation of the unusual dose-responses to BZ exposure indicates cellular over-compensation and reprogramming to overcome toxicity and to promote survival. However, these abnormal mechanisms also promote the induction of leukemia. Further investigations indicate that the current exposure limits for workers to BZ are unacceptable. Based on these studies, the new exposure limits should be less than 0.07 ppm rather than the current 1 ppm. This review also emphasizes the need to conduct appropriate bioassays, and to provide more reliable decisions on health hazards as well as on exposure limits for workers. In addition, it is important to use scientific data to provide significantly improved risk assessment, i.e., shifting from a population- to an individual-based risk assessment.


Assuntos
Benzeno , Exposição Ocupacional , Humanos , Benzeno/toxicidade , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/análise , Dano ao DNA , Reparo do DNA , Medição de Risco
2.
J Occup Environ Med ; 65(12): e759-e763, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37757745

RESUMO

OBJECTIVES: To explore the differences in the increase of systolic blood pressure (SBP) and diastolic blood pressure (DBP) in 3 consecutive years among lead (Pb) workers. METHODS: Four hundred forty-eight Pb workers were enrolled in this repeated-measure study. Blood Pb, SBP, and DBP were measured in 2015 to 2017. Repeated measure of analysis of variance was used to compare the differences in the increase of SBP and DBP. RESULTS: The mean SBP values were 124.0/125.5/126.9 mm Hg, and the mean DBP values were 75.4/77.4/77.8 mm Hg from 2015 to 2017. The differences in the increase of SBP and DBP were 2.94/2.42 mm Hg during the 3-year period. The average annual increase of SBP or DBP showed an upward trend in different Pb dose groups ( F = 4.904, P = 0.002; F = 3.612, P = 0.013). CONCLUSIONS: Lead exposure caused average annual increases in SBP and DBP with 0.98 and 0.81 mm Hg, which provided basic data for health surveillance.


Assuntos
Hipertensão , Chumbo , Humanos , Pressão Sanguínea , China/epidemiologia , Hipertensão/epidemiologia
3.
Int J Environ Health Res ; : 1-11, 2023 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-37669754

RESUMO

Few studies have been conducted that use biomarkers as early warning signals for noise-associated health hazards. To explore potentially effective biomarkers for noise-exposed populations, we recruited 218 noise-exposed male workers in China. We calculated cumulative noise exposure (CNE) through noise intensity and noise-exposed duration. When the model was fully adjusted, ln-transformed relative mitochondrial DNA copy number (mtDNAcn) decreased by 0.014 (95% confidence interval (CI): -0.026, -0.003) units with each 1 dB(A)∙year increase in CNE levels. CNE was further included in the model as a grouping variable, and the results showed a negative dose-effect relationship between relative mtDNAcn and CNE (P-trend = 0.045). However, we did not find a correlation between CNE and micronucleus (MN) frequencies. Our findings suggest that CNE in workers was associated with a decrease in relative mtDNAcn which may provide a potential biomarker for noise and for certain health risk but not with MN frequencies.

4.
Environ Pollut ; 330: 121765, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37142205

RESUMO

Based on previous exposure studies, benzene (BZ) has been classified as a human carcinogen and occupational exposure limit (OELs) for BZ has been set to be about 1 ppm around the world. However, health hazards have still been reported with exposure below the OEL. Thus, the OEL needs to be updated to reduce health risk. The overall aim of our study was therefore to generate new OEL for BZ via a benchmark dose (BMD) approach and based on quantitative and multi-endpoint genotoxicity assessments. Genotoxicities were determined using the novel human PIG-A gene mutation assay, the micronucleus (MN) test and the COMET assay in benzene-exposed workers. Among the 104 workers with below current OELs, they exhibited significantly higher PIG-A mutant frequencies (MFs) (15.96 ± 14.41 × 10-6) and MN frequencies (11.55 ± 6.83‰) than those among the controls (PIG-A MFs: 5.46 ± 4.56 × 10-6, MN frequencies: 4.51 ± 1.58 ‰), but no difference in the COMET assay. A significant association was also observed between BZ exposure doses and PIG-A MFs and MN frequencies (P < 0.001). Our results indicate that health hazards were induced among workers with below OEL exposures. Based on results from the PIG-A and MN assays, the lower confidence limit of the BMD (BMDL) were calculated to be 8.71 mg/m3-year and 0.44 mg/m3-year, respectively. Based on these calculations, the OEL for BZ was determined to be lower than 0.07 ppm. This value can be considered by regulatory agencies to set new exposure limits and to better protect workers.


Assuntos
Benzeno , Exposição Ocupacional , Humanos , Benzeno/toxicidade , Benchmarking , Exposição Ocupacional/análise , Dano ao DNA , Testes para Micronúcleos , China
5.
Environ Pollut ; 316(Pt 1): 120528, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36341824

RESUMO

Studies have shown that lead (Pb) exposure caused genotoxicity, however, the underlying mechanisms remain unclear. A mechanism may be via DNA methylation which is one of the most widely studied epigenetic regulations for cellular activities. Whether this is involved in Pb-induced genotoxicity has rarely been studied. Our study aimed to examine whether DNA methylation was associated with Pb exposure and genotoxicity, and to explore its potential mediating roles. A total of 250 Pb-exposed workers were enrolled. Blood lead levels (BLLs) and genotoxic biomarkers (Micronuclei and Comet) were analyzed. Methylation levels at CpG sites of LINE1 and Alu and promoter region of P53, BRCA1, TRIM36 and OGG1 were measured by pyrosequencing. Generalized linear model (GLM) combined with restricted cubic splines (RCS) were used to analyze relationships between Pb exposure, DNA methylation and genotoxicity. Mediation effect was used to explore mediating roles of DNA methylation. The distribution of BLLs was right-skewed and showed wide ranges from 23.7 to 636.2 µg/L with median (P25, P75) being 218.4 (106.1, 313.9) µg/L among all workers. Micronuclei frequencies showed Poisson distribution [1.94 ± 1.88‰] and Comet tail intensity showed normal distribution [1.69 ± 0.93%]. GLM combined with RCS showed that Alu methylation was negatively associated with BLLs, while P53 and OGG1 methylation were positively associated with BLLs. Micronuclei were negatively associated with Alu and TRIM36 methylation but positively with P53 methylation. Comet was positively associated with P53 and BRCA1 methylation. Mediation effect showed that Alu methylation mediated 7% effects on association between Pb exposure and micronuclei, whereas, P53 methylation mediated 14% and BRCA1 mediated 9% effects on association between Pb exposure and Comet. Our data show that Pb exposure induced changes of global and gene-specific DNA methylation which mediated Pb-induced genotoxicity.


Assuntos
Chumbo , Exposição Ocupacional , Humanos , Chumbo/toxicidade , Metilação de DNA , Proteína Supressora de Tumor p53/genética , Dano ao DNA
6.
Mutat Res Rev Mutat Res ; 790: 108427, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35688302

RESUMO

Combinations of genetic and environmental factors are responsible for the development of many human diseases, such as cancer, as demonstrated using various biomarkers. Within this scenario, DNA repair holds a gate-keeper position which determines outcomes after appearance of DNA damage and, therefore, adverse cellular consequences, e.g., initiation of carcinogenesis. DNA repair deficiency and some of the subsequent events can be validated from studies using live cells from cancer patients. However, these deficiencies/events are difficult to demonstrate in live cells from normal individuals because individual variations in DNA repair capacities (DRC) are too low to be measured easily. Such lack of information has been hindering progress in developing personalized disease prevention and intervention protocols, especially among exposed populations. However, using a variety of challenge assays as biomarkers, variations in individual's DRC can be amplified in live cells and be determined. Furthermore, evidence indicates that DRC are not only inherited but can also be modified by environmental factors (e.g., nutritional status and exposure to genotoxic substances). Using these challenge assays, e.g., in live lymphocytes, individual's DRC can be holistically and functionally determined as well as quantitated. With the more precise information, assessment of health risk can be better determined on an individual rather than on a population basis. This review provides a succinct summary on the development and application of recent challenge assays in lymphocytes which can provide measurements of individuals' DRC, and on the latest data for more precise disease prevention and intervention.


Assuntos
Reparo do DNA , Neoplasias , Humanos , Reparo do DNA/genética , Linfócitos , Dano ao DNA/genética , Biomarcadores , Medição de Risco , DNA , Testes para Micronúcleos/métodos
7.
Environ Pollut ; 304: 119252, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35385786

RESUMO

Lead (Pb) exposure can induce DNA damage and alter DNA methylation but their inter-relationships have not been adequately determined. Our overall aims were to explore such relationships and to evaluate underlying epigenetic mechanisms of Pb-induced genotoxicity in Chinese workers. Blood Pb levels (BLLs) were determined and used as individual's Pb-exposure dose and the Comet assay (i.e., % tail DNA) was conducted to evaluate DNA damage. In the screening assay, 850 K BeadChip sequencing was performed on peripheral blood from 10 controls (BLLs ≤100 µg/L) and 20 exposed workers (i.e., 10 DNA-damaged and 10 DNA-undamaged workers). Using the technique, differentially methylated positions (DMPs) between the controls and the exposed workers were identified. In addition, DMPs were identified between the DNA-undamaged and DNA-damaged workers (% tail DNA >2.14%). In our validation assay, methylation levels of four candidate genes were measured by pyrosequencing in an independent sample set (n = 305), including RRAGC (Ras related GTP binding C), USP1 (Ubiquitin specific protease 1), COPS7B (COP9 signalosome subunit 7 B) and CHEK1 (Checkpoint kinase 1). The result of comparisons between the controls and the Pb-exposed workers show that DMPs were significantly enriched in genes related to nerve conduction and cell cycle. Between DNA-damaged group and DNA-undamaged group, differentially methylated genes were enriched in the pathways related to cell cycle and DNA integrity checkpoints. Additionally, methylation levels of RRAGC and USP1 were negatively associated with BLLs (P < 0.05), and the former mediated 19.40% of the effect of Pb on the % tail DNA. These findings collectively indicated that Pb-induced DNA damage was closely related to methylation of genes in cell cycle regulation, and methylation levels of RRAGC were involved in Pb-induced genotoxicity.


Assuntos
Metilação de DNA , Exposição Ocupacional , DNA , Dano ao DNA , Humanos , Chumbo/toxicidade
8.
BMC Geriatr ; 21(1): 536, 2021 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-34627157

RESUMO

BACKGROUND: The cognitive impact of changes in late-life blood pressure is less clear. We aimed to investigate the association between late-life blood pressure changing pattern and risk of cognitive impairment. METHODS: Using data from the community-based Chinese Longitudinal Healthy Longevity Survey, change in systolic (SBP) or diastolic (DBP) blood pressure was calculated as the difference between follow-up and baseline, cognitive impairment was defined based on both the Mini-Mental State Examination and education level. The generalized additive model with penalized spline and multivariate logistic regression model were used, respectively, to examine the associations between continuous and categorized blood pressure changes with cognitive impairment at the follow-up wave. RESULTS: A total of 8493 Chinese elderly without cognitive impairment were included, with mean (standard deviation) age 80.6 (10.7) years. U-shaped associations between late-life blood pressure changes and risk of cognitive impairment were found, with only stable optimal blood pressure related to the lowest risk. For participants with baseline SBP around 130-150 mmHg, the adjusted odds ratio was 1.48 (1.13-1.93) for increasing follow-up SBP (> 150 mmHg), 1.28 (1.02-1.61) for decreasing follow-up SBP (< 130 mmHg), compared to stable follow-up SBP (130-150 mmHg). For participants with relative lower baseline DBP (< 80 mmHg), increasing their DBP to 80-90 mmHg during follow-up was associated with lower cognitive impairment risk (0.73 (0.58-0.93)), compared to steady low follow-up DBP (< 80 mmHg). Sex-specific analysis suggested that men were more vulnerable in term of SBP change. CONCLUSIONS: Adhering to a stable optimal level of blood pressure in late-life is related to lower risk of cognitive impairment in Chinese elderly.


Assuntos
Disfunção Cognitiva , Hipertensão , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea , China/epidemiologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/epidemiologia , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Estudos Longitudinais , Masculino , Razão de Chances
9.
BMC Geriatr ; 21(1): 562, 2021 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-34663235

RESUMO

BACKGROUND: Blood pressure targets for oldest-old people have been long debated due to the concern that more stringent targets are associated with increased mortality. We aimed to investigate the association between changes of late-life systolic blood pressure (SBP), mean SBP and SBP variability (SBPV), and all-cause mortality in oldest-old. METHODS: Based on the community-based Chinese Longitudinal Healthy Longevity Survey with follow-up conducted in the 3-year interval, we assembled a retrospective cohort of 6639 participants ≥ 80 years with available blood pressure measurements at baseline and second wave. The primary exposures were mean SBP and SBPV (defined as the annual difference in SBP divided by mean SBP) measured between baseline and second wave. The primary outcome was all-cause mortality assessed from the second wave. RESULTS: During 21443.1 person-years of follow-up, 4622 death was recorded. U-shaped associations of mortality with mean SBP and SBPV were identified; the value of 137 mmHg and 4.0 %/year conferred the minimum mortality risk, respectively. The associations of a larger SBPV with an increased mortality risk were observed for both rises and large falls in SBP. The hazard ratio was 1.11 (comparing lowest versus middle quintile; 95 % CI: 1.01, 1.22) with large falls in SBPV and 1.08 (comparing highest versus middle quintile; 95 % CI: 0.98, 1.18) with large rises in SBPV. CONCLUSIONS: U-shaped associations between late-life SBP and SBPV and all-cause mortality were found. Our study suggests that a stable SBP level in the middle range is related to lower mortality risk in the oldest-old.


Assuntos
Hipertensão , Idoso de 80 Anos ou mais , Pressão Sanguínea , China/epidemiologia , Humanos , Estudos Longitudinais , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco
10.
Environ Mol Mutagen ; 62(7): 428-434, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34269489

RESUMO

Perturbation of epigenetic regulation is a well-established mechanism for cancer but its role for lead (Pb)-associated toxicity has not been adequately investigated. We aimed to investigate whether occupational Pb exposure is associated with micronuclei (MN) frequency and to further explored the mediating roles of epigenetic gene regulation. All the Pb-exposed workers recruited from a Chinese acid battery factory, blood lead levels (BLLs) and MN frequency in lymphocytes were measured. In addition, methylation levels of seven genes (Line-1, RASSF1A, RUNX3, p16, CYP26C1, hMLH1, p15) were examined among 230 workers. Robust Poisson regression model was used to investigate the association between BLLs and MN frequency. Mediation analysis was used to explore the mediating role of specific DNA methylation. Among total 677 participants, 71% were male, median BLLs was 229.1 µg/L (P25  = 155.5, P75  = 319.3; ranged from 8.9 to 647.7 µg/L), mean MN frequency was 2.5‰ (SD = 1.8‰; ranged from 0 to 9‰). Results from base model, adjusted for age, sex, and body mass index, showed that MN frequency would increase 1.38 (95%confidential interval: 1.34, 1.43) per 100 µg/L increment in BLLs. Using categorized exposure variable analyses, a BLLs dose-response increase in MN frequency was observed: 2.74 (2.13, 3.51), 3.43 (2.73, 4.32), 4.41 (3.89, 5.01) to 6.86 (6.02, 7.81). Mediation analysis indicated that Line-1 methylation significantly mediated 3.6% of the association of BLLs with MN frequency. Occupational Pb exposure induces MN frequency in a dose-response relationship. Part of this association was mediated by Line-1 promotor methylation.


Assuntos
Dano ao DNA , Metilação de DNA , Chumbo/efeitos adversos , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Doenças Profissionais/epidemiologia , Exposição Ocupacional/efeitos adversos , Regiões Promotoras Genéticas , Adulto , China/epidemiologia , Estudos Transversais , Citocinese , Epigênese Genética , Feminino , Humanos , Masculino , Testes para Micronúcleos , Doenças Profissionais/induzido quimicamente , Exposição Ocupacional/análise
11.
J Occup Environ Med ; 63(7): e408-e415, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34184658

RESUMO

OBJECTIVE: To determine the effect of mitochondrial DNA copy number (mtDNAcn) as a biomarker of benzene exposure. METHODS: A total of 294 benzene-exposed workers and 102 controls were recruited. Biomarkers of mtDNAcn, cytokinesis-block micronucleus (MN) frequency, and peripheral blood white blood cells (WBC) were detected. Eighteen polymorphism sites in DNA damage repair and metabolic genes were analyzed. RESULTS: Benzene exposure increased mtDNAcn and indicated a dose-response relationship (P < 0.001). mtDNAcn was negatively correlated with WBC count and DNA methylation and positively correlated with MN frequency. The AG type in rs1695 interacted with benzene exposure to aggravate mtDNAcn (ß = 0.006, 95% CI: 0, 0.012, P = 0.050). rs13181, rs1695, rs1800975, and GSTM1 null were associated with benzene-induced mtDNAcn. Rs1695 interacted with benzene to increase mitochondrial damage. CONCLUSIONS: Benzene exposure increases mtDNAcn levels in benzene-exposed workers.


Assuntos
Benzeno , Exposição Ocupacional , Benzeno/análise , Benzeno/toxicidade , Variações do Número de Cópias de DNA , DNA Mitocondrial/genética , Interação Gene-Ambiente , Humanos , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/análise
12.
Environ Int ; 151: 106448, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33618327

RESUMO

BACKGROUND: Lead (Pb) is known to induce detrimental health effects in exposed populations, including hematotoxicity and genotoxicity. Complete blood count (CBC) is a cost-effective and easy way to determine toxicity, and variations in proportion of different types of leukocytes: neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) are further evidence of hematotoxicity. However, few studies have been conducted to systematically evaluate effects of occupational Pb exposure on NLR and LMR, and their associations with genotoxicity. OBJECTIVES: Our study was aimed to systematically assess the effects of current occupational Pb exposure on NLR and LMR, and their associations with genotoxicity. METHODS: Our investigation was performed on 1176 workers from a newly built battery factory in North China. The workers had just entered their current job position in recent years and most of them had no previous history of occupational exposure to Pb. Blood lead levels (BLLs) and leukocytes indices were detected for all participants. Cytokinesis-blocked micronucleus assay (MN; n = 675) and alkaline comet assay (% tail DNA; n = 869) were used to assess genotoxicity. Multivariate linear and Poisson regression analyses were conducted to examine associations between leukocytes indices, genotoxic biomarkers and BLLs with adjustment for covariates. Spearman correlation and mediation analyses were used to investigate relationships between NLR and genotoxicity. RESULTS: Among all the exposed workers, NLR increased with increasing BLLs. However, WBC and LMR did not change significantly. Significant and dose-dependent increases in both MN frequencies and % tail DNA were observed among groups with different exposure doses. Compared with the normal NLR group (1.48 ≤ NLR < 4.58), the high NLR group (NLR ≥ 4.58) had higher % tail DNA. In addition, there was a significant and positive association between NLR and % tail DNA among all the workers, and % tail DNA mediated 15% of the effect of Pb on increasing NLR. CONCLUSION: Our large-scale population study shows that Pb exposure increased NLR and induced genotoxicity. There was an association between elevated NLR and DNA damage. In addition, the mediation effect of % tail DNA on the relationship between BLLs and NLR provided mechanistic evidence that certain mechanisms, e.g. inflammation, may be involved in elevation of NLR from Pb exposure. Therefore, NLR may be a convenient and sensitive biomarker for indication of Pb toxicity. Further studies are needed to validate the proposed mechanism and NLR as a biomarker.


Assuntos
Chumbo , Exposição Ocupacional , China , Dano ao DNA , Humanos , Chumbo/toxicidade , Linfócitos , Testes para Micronúcleos , Neutrófilos , Exposição Ocupacional/efeitos adversos
13.
Sci Total Environ ; 765: 142740, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33071125

RESUMO

Mechanisms for hematotoxicity and health effects from exposure to low doses of benzene (BZ) remain to be identified. To address the information gap, our investigation was focused onto using appropriate populations and cell cultures to investigate novel BZ-induced effects such as disruption of DNA repair capacity (DRC). From our study, abnormal miRNAs were identified and validated using lymphocytes from 56 BZ-poisoned workers and 53 controls. In addition, 173 current BZ-exposed workers and 58 controls were investigated for key miRNA expression using RT-PCR and for cellular DRC using a challenge assay. Subsequently, the observed activities in lymphocytes were verified using human HL-60 (p53 null) and TK6 (p53 wild-type) cells via 1,4-benzoquinone (1,4-BQ) treatment and miR-222 interferences. The targeting of MDM2 by miR-222 was validated using a luciferase reporter. Our results indicate induction of genotoxicity in lymphocytes from workers with low exposure doses to BZ. In addition, miR-222 expression was up-regulated among both BZ-poisoned and BZ-exposed workers together with inverse association with DRC. Our in vitro validation studies using both cell lines indicate that 1,4-BQ exposure increased expression of miR-222 and Comet tail length but decreased DRC. Loss of miR-222 reduced DNA damage, but induced S-phase arrest and apoptosis. However, silencing of MDM2 failed to activate p53 in TK6 cells. In conclusion, our in vivo observations were confirmed by in vitro studies showing that BZ/1,4-BQ exposures caused genotoxicity and high expression of miR-222 which obstructed expression of the MDM2-p53 axis that led to failed activation of p53, abnormal DRC and serious biological consequences.


Assuntos
Benzeno , MicroRNAs , Apoptose , Benzeno/toxicidade , Dano ao DNA , Reparo do DNA , Humanos , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
14.
Environ Pollut ; 271: 116329, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33370612

RESUMO

Limited data were on the acute respiratory responses in the elderly in response to personal exposure of particulate matter (PM). In order to evaluate the changes of airway inflammation and pulmonary functions in the elderly in response to individual exposure of particles (PM1.0, PM2.5 and PM10), we analyzed 43 elderly subjects with either asthma, chronic obstructive pulmonary disease (COPD) or Asthma COPD Overlap (ACO) and 40 age-matched subjects without asthma nor COPD in an urban community in Shanghai, China. Data were collected at the baseline and in 6 follow-ups from August 2016 to December 2018, once every 3 months except for the last twice with a 6-month interval. In each follow-up, pulmonary functions, fractional exhaled nitric oxide (FeNO), 7-day continuous personal exposure to airborne particles were measured. Multivariate linear mixed effect regression models were applied to investigate the quantitative changes of pulmonary functions and FeNO in two respective groups. The results showed that on average 4.7 follow-up visits were completed in each participant. In subjects with CRDs, an inter-quartile range (IQR) increase of personal exposure to PM1.0, PM2.5 and PM10 was significantly associated with an average increase of FeNO(Lag1) of 6.7 ppb (95%CI 1.2, 9.9 ppb), 6.2 ppb (95%CI 1.5, 12.0 ppb) and 5.6 ppb (95%CI 1.5, 11.0 ppb), respectively, and an average decrease of FEV1(Lag2) of -3.6 L (95%CI -6.0, -1.1 L), -3.6 L (95%CI -6.4, -0.8 L) and -3.2 L (95%CI -5.8, -0.6 L), respectively, in the single-pollutant model. These associations remained consistent in the two-pollutant models adjusting for gaseous air pollutants. Stratified analysis showed that subjects with lower BMI, females and non-allergies were more sensitive to particle exposure. No robust significant effects were observed in the subjects without CRDs. Our study provided data on the susceptibility of the elderly with CRDs to particle exposure of PM1.0 and PM2.5, and the modification effects by BMI, gender and history of allergies.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Asma , Doença Pulmonar Obstrutiva Crônica , Idoso , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , China , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Feminino , Humanos , Material Particulado/análise
15.
Environ Int ; 145: 106129, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32950787

RESUMO

BACKGROUND: Excessive lead exposure is associated with adverse health effects. However, there is a lack of systematic investigation using large populations to ascertain acceptable exposure limits. OBJECTIVES: Our study was aimed to identify human exposure-response relationships between lead exposure and health-related outcomes, and to determine a benchmark dose (BMD). METHODS: A total of 1896 participants from a lead-acid battery plant were recruited. Blood lead levels (BLLs) were detected for all participants. Hematological parameters (n = 1896), micronuclei (MN) frequencies (n = 934), and relative telomere length (rTL) (n = 757) were also determined. Multivariate linear/Poisson regression analyses were performed to examine associations between BLLs and these health outcomes. Restricted cubic splines were used to identify dose-response relationships. Three BMD approaches were used to calculate BMD and its 95% lower confidence limit (BMDL). RESULTS: Among all participants, BLLs show a right-skewed distribution (median, 185.40 µg/L; 25th - 75th percentile, 104.63-271.70 µg/L). There existed significant differences for red blood cell (RBC), hemoglobin (Hb), MN and rTL among different BLL dose groups. After adjusting for possible confounders, all indicators were significantly associated with BLLs. Restricted cubic splines show that there were linear dose-response relationships for RBC and Hb with BLLs, while non-linear for MN and rTL. Results from the three BMD approaches indicate that the dichotomous models were better than continuous models to calculate BMD and BMDL of BLLs. The conservative BMDL obtained from RBC data was 135 for total, 104 for male and 175 µg/L for female. The corresponding BMDL obtained from Hb data was 105 for total, 116 for male and 70 µg/L for female. As for MN data, the BMDL estimate was 66 for total, 69 for male and 64 µg/L for female. Finally, the BMDL from rTL data was 35 for total, 32 for male and 43 µg/L for female. CONCLUSIONS: Our data show significant dose-response relationships between lead exposure and expressions of hematological toxicity and genotoxicity. The new BMDLs of 135 and 105 µg/L based on RBC and Hb, and even more strict level of 66 and 35 µg/L based on MN and rTL are lower than current exposure limits in China. Therefore, the four values can be considered as novel exposure limits. In addition, sex effect should be taken into account when setting occupational health standard. Considering that different biomarkers have different sensitivities, better understanding their relationships will certainly improve the current emphasis on precision health risk assessment.


Assuntos
Benchmarking , Chumbo , China , Feminino , Humanos , Chumbo/toxicidade , Masculino , Medição de Risco , Telômero
16.
Data Brief ; 31: 105869, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32637486

RESUMO

In this paper, we present an occupational dataset to evaluate benzene exposure on the effective biomarkers of genetic damage, indicated as cytokinesis-block micronucleus (MN) frequency, hematotoxicity, indicated as white blood cells (WBC) counts, and molecular marker of telomere length (TL). And we further to eliminate the mechanism of benzene induced damage. Then evaluate the effects of sites polymorphism in environmental response genes, including 18 sites in metabolic and DNA repair genes, and the interaction between gene polymorphism and benzene exposure. This dataset is supplementary to the submitted research by [1] focused on the biomarkers TL, and a detailed description of the subjects sampling, biomarkers detection, data analysis and discussion are discussed in detail.

17.
J Occup Environ Med ; 62(7): e308-e317, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32730034

RESUMO

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.


Assuntos
Benzeno/intoxicação , Leucemia Mieloide Aguda/genética , RNA Longo não Codificante/genética , Adulto , Aberrações Cromossômicas , Feminino , Regulação da Expressão Gênica , Humanos , Leucemia Mieloide Aguda/induzido quimicamente , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional/efeitos adversos , RNA Mensageiro/genética
18.
Chemosphere ; 255: 126841, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32416388

RESUMO

Benzene is a globally occurring environmental and occupational pollutant that causes leukemia. To better understand telomere length (TL) as a function of benzene toxicity, we recruited 294 shoe-making workers and 102 controls from Wenzhou, China in 2011. Biomarkers of TL, cytokinesis-block micronucleus (MN) frequency, and white blood cells (WBC) were measured. In total, 18 polymorphic sites in environmental response genes, including metabolic and DNA repair genes, were analyzed. Results indicate that benzene exposure led to a longer TL at a threshold of 32 mg/m3-year of cumulative exposure dose (CED). Furthermore, the TL was longer in members of the damaged group, when evaluated for MN frequency (P < 0.001) and reduced WBC (P < 0.001), than in those of the normal group. Workers carrying genotype TT (ß = 0.32, P = 0.042) in rs3212986 of ERCC1 and genotype TC (ß = 0.24, P = 0.082) in rs1051740 of mEH exon3 were associated with a longer TL as compared to the wild-type group. TA (ß = -0.53, P < 0.001) in rs6413432 of CYP2E1 was associated with a shorter TL. Benzene exposure interacted with the TA type in rs6413432 (ß = 0.003, 95% CI: 0, 0.006, P = 0.042) and the CC type in rs1051740 (ß = 0.007, 95% CI: 0.001, 0.013, P = 0.015) after adjusting for confounding factors. Our results indicate that benzene induces an increase in TL at a threshold of CED ≥32mg/m3-year. Rs1051740, rs3212986, and rs6413432 were found to be involved in benzene-induced telomere growth; in particular, rs1051740 and rs6413432 interacted with the benzene exposure, resulting in an extended TL.


Assuntos
Poluentes Ocupacionais do Ar/análise , Benzeno/análise , Exposição Ocupacional/análise , Telômero , Adulto , Poluentes Ocupacionais do Ar/toxicidade , Benzeno/toxicidade , China , Citocromo P-450 CYP2E1/genética , Feminino , Genótipo , Humanos , Masculino , Polimorfismo Genético , Sapatos
19.
Environ Mol Mutagen ; 61(6): 611-621, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32285465

RESUMO

The rodent Pig-a gene mutation assay has demonstrated remarkable sensitivity in identifying in vivo mutagens, while much less is known about the value of the human PIG-A assay for risk assessment. To obtain more evidence of its potential as a predictive biomarker for carcinogen exposure, we investigated PIG-A mutant frequencies (MFs), along with performing the Comet assay and micronucleus (MN) test, in 267 workers occupationally exposed to lead. Multivariate Poisson regression showed that total red blood cell PIG-A MFs were significantly higher in lead-exposed workers (10.90 ± 10.7 × 10-6 ) than in a general population that we studied previously (5.25 ± 3.6 × 10-6 ) (p < .0001). In contrast, there was no increase in lymphocyte MN frequency or in DNA damage as measured by percentage comet tail intensity in whole blood cells. Current year worker blood lead levels (BLL), an exposure biomarker, were elevated (232.6 ± 104.6 µg/L, median: 225.4 µg/L); a cumulative blood lead index (CBLI) also was calculated based on a combination of current and historical worker BLL data. Chi-square testing indicated that PIG-A MFs were significantly related to CBLI (p = .0249), but independent of current year BLL (p = .4276). However, % comet tail intensity and MN frequencies were better associated with current year BLL than CBLI. This study indicates that the PIG-A assay could serve as biomarker to detect the genotoxic effects of lead exposure and demonstrates that a battery of genotoxicity biomarkers having mechanistic complementarity may be useful for comprehensively monitoring human carcinogenic risk.


Assuntos
Chumbo/toxicidade , Proteínas de Membrana/genética , Mutagênicos/toxicidade , Exposição Ocupacional/efeitos adversos , Adulto , Ensaio Cometa/métodos , Dano ao DNA/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Feminino , Humanos , Masculino , Testes para Micronúcleos/métodos , Pessoa de Meia-Idade , Mutação/efeitos dos fármacos , Taxa de Mutação
20.
Environ Mol Mutagen ; 61(8): 786-796, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32329128

RESUMO

Benzene is a global pollutant and has been established to cause leukemia. To better understand the role of DNA methylation in benzene toxicity, peripheral blood mononuclear cells were collected from six benzene-poisoning patients and six matched controls for genome-wide DNA methylation screening by Illumina Infinium Methylation 450 BeadChip. The Gene Chip Human Gene 2.0 ST Array (Affymetrix) was used to analyze global mRNA expression. Compared with the corresponding sites of controls, 442 sites in patients were hypermethylated, corresponding to 253 genes, and 237 sites were hypomethylated, corresponding to 130 genes. The promoter methylation and mRNA expression of CSF3R, CREB5, and F2R were selected for verification by bisulfite sequencing and real-time PCR in a larger data set with 21 cases and 23 controls. The results indicated that promoter methylation of CSF3R (p = .005) and F2R (p = .015) was significantly higher in cases than in controls. Correlation analysis showed that the promoter methylation of CSF3R (p < .001) and F2R (p < .001) was highly correlated with its mRNA expression. In the poisoning cases, neutrophil percentage was significantly different among the high, middle, and low CSF3R-methylation groups (p = .002). In particular, the neutrophil percentage in the high CSF3R-methylation group (48.10 ± 9.63%) was significantly lower than that in the low CSF3R-methylation group (59.30 ± 6.26%) (p = .012). The correlation coefficient between promoter methylation in CSF3R and the neutrophil percentage was -0.445 (p = .020) in cases and - 0.398 (p = .060) in controls. These results imply that hypermethylation occurs in the CSF3R promoter due to benzene exposure and is significantly associated with a reduction in neutrophils.


Assuntos
Benzeno/toxicidade , Metilação de DNA , Neutrófilos/efeitos dos fármacos , Regiões Promotoras Genéticas , Receptores de Fator Estimulador de Colônias/genética , Adolescente , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neutrófilos/citologia , Exposição Ocupacional
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