RESUMEN
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.
Asunto(s)
Benceno/efectos adversos , ADN (Citosina-5-)-Metiltransferasas/biosíntesis , Metilación de ADN/efectos de los fármacos , Silenciador del Gen/efectos de los fármacos , Hidroquinonas/toxicidad , Leucemia Mieloide Aguda/inducido químicamente , MicroARNs/metabolismo , Enfermedades Profesionales/inducido químicamente , Exposición Profesional/efectos adversos , Estudios de Casos y Controles , Línea Celular Transformada , Línea Celular Tumoral , ADN (Citosina-5-)-Metiltransferasas/genética , Inducción Enzimática , Regulación Enzimológica de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Leucemia Mieloide Aguda/enzimología , Leucemia Mieloide Aguda/genética , MicroARNs/genética , Enfermedades Profesionales/enzimología , Enfermedades Profesionales/genética , Regiones Promotoras Genéticas , Medición de Riesgo , ADN Metiltransferasa 3BRESUMEN
This study evaluated the associations between job strain and arginase I in 378 healthy Japanese factory workers by a cross-sectional study measuring nitric oxide (NO)-related parameters (arginase I, L-arginine, exhaled nitric oxide (FeNO), and NOx), clinical parameters, and job strain using a Japanese version of the Job Content Questionnaire by Karasek. Arginase I and FEV1% were negatively correlated with job strain and positively correlated with job control and social support. FeNO and hs-CRP were negatively correlated with job strain. Multiple regression analysis showed negative association of arginase I with job strain and positive association with job control and social support in females. It is concluded that serum levels of arginase I may be useful biomarkers for the diagnosis of job stress in healthy female workers, although many factors can be influencing the data.
Asunto(s)
Arginasa/sangre , Óxido Nítrico/sangre , Enfermedades Profesionales/sangre , Estrés Psicológico/sangre , Adulto , Biomarcadores/sangre , Estudios Transversales , Femenino , Personal de Salud , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Profesionales/enzimología , Estrés Psicológico/enzimologíaRESUMEN
ALDH2 is involved in the metabolism of styrene, a widely used industrial material, but no data are available regarding the influence of this enzyme on the metabolic fate as well as toxic effects of this chemical. In this study, we recruited 329 workers occupationally exposed to styrene and 152 unexposed controls. DNA strand breaks, DNA-base oxidation in leukocytes and urinary 8-hydroxydeoxyguanosine (8-OH-dG) were assayed as biomarkers to measure genotoxic effects. Meanwhile, we examined the genetic polymorphisms, including ALDH2, EXPH1, GSTM1, GSTT1 and CYP2E1, and also analyzed the levels of styrene exposure through detecting urinary styrene metabolites and styrene concentration in air. In terms of DNA damage, the three genotoxic biomarkers were significantly increased in exposed workers as compared with controls. And the styrene-exposed workers with inactive ALDH2 *2 allele were subjected to genotoxicity in a higher degree than those with ALDH2 *1/*1 genotype. Also, lower levels of urinary styrene metabolites (MA + PGA) were observed in styrene-exposed workers carrying ALDH2 *2 allele, suggesting slower metabolism of styrene. The polymorphisms of other enzymes showed less effect. These results suggested that styrene metabolism and styrene-induced genotoxicity could be particularly modified by ALDH2 polymorphisms. The important role of ALDH2 indicated that the accumulation of styrene glycoaldehyde, a possible genotoxic intermediate of styrene, could account for the genotoxicity observed, and should be taken as an increased risk of cancer.
Asunto(s)
Aldehído Deshidrogenasa Mitocondrial/metabolismo , Enfermedades Profesionales/inducido químicamente , Enfermedades Profesionales/enzimología , Estireno/envenenamiento , Adulto , Aldehído Deshidrogenasa Mitocondrial/genética , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Pruebas de Mutagenicidad , Enfermedades Profesionales/genética , Enfermedades Profesionales/patología , Exposición Profesional , Polimorfismo Genético , Estireno/farmacocinéticaRESUMEN
ADAM33 represents an important gene of susceptibility for lung function impairment. This work aimed to evaluate the association between genetic polymorphism of ADAM33 at four single nucleotide polymorphisms (T1, T2, S1, and Q1) and arginase activity with respiratory functions impairment in wood workers. The study was done to compare ventilatory functions and arginase activity of 82 wood workers and 81 controls. Genotyping was determined by using the polymerase chain restriction fragment length polymorphism method. Forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), and peak expiratory flow rate (PEF) of the workers were significantly reduced compared with the controls. T1 single nucleotide polymorphism (SNP) was associated with obvious decline in the FEV1, FVC, and PEF in wood workers, while T2 SNP was associated with decline in FEV1 and PEF. A significant increase in arginase activity was found in T2 and S1 SNPs of the exposed workers. Increase in duration of exposure was correlated with the decline in ventilatory functions. This inverse correlation was significant for pulmonary function indices in AA and GG genotypes of T1 and T2, respectively. Moreover, significance was detected for FVC and FEV1 in AA and GA genotypes of S1 and Q1. A positive correlation between arginase activity and duration of exposure was found to be significant in GG genotype of S1 SNP. An association between ADAM33 gene polymorphism and impaired lung functions was detected in wood dust-exposed workers. Arginase activity may play an associated important role in increasing this impairment in wood workers.
Asunto(s)
Proteínas ADAM/genética , Contaminantes Ocupacionales del Aire/toxicidad , Arginasa/metabolismo , Polvo , Enfermedades Profesionales/inducido químicamente , Polimorfismo de Nucleótido Simple , Insuficiencia Respiratoria/inducido químicamente , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Enfermedades Profesionales/enzimología , Enfermedades Profesionales/genética , Exposición Profesional/efectos adversos , Pruebas de Función Respiratoria , Insuficiencia Respiratoria/enzimología , Insuficiencia Respiratoria/genética , Madera/químicaRESUMEN
UNLABELLED: This study is to explore the effect of ALAD polymorphism on hematopoietic, hepatic and renal toxicity from lead in occupational exposure workers. METHODS: We conducted a cross-sectional study on 156 workers with occupational exposure to lead between 2002 and 2007. The results of laboratory examinations were analyzed. RESULTS: The authors found that workers with the ALAD 1-1 genotype were associated with higher blood lead level than those with the ALADl-2 genotype. Blood and urine lead levels were much higher in storage battery workers than in cable workers. The urine ALA and blood ZPP levels in workers with the ALAD 1-1 genotype were higher than those with the ALADl-2 genotype. The serum Cr level in workers with the ALADl-1 genotype was much higher than those with the ALADl-2 genotype especially in higher lead exposure level. CONCLUSIONS: The ALAD-2 protein might modify the kinetics of lead in blood at a relatively higher blood lead level and protect against hematopoietic, hepatic and renal toxicity from lead. Urine ALA, blood ZPP and serum Cr levels might be considered as effective biological monitoring partners of lead induced hematopoietic and renal toxicology.
Asunto(s)
Pueblo Asiatico/genética , Hematopoyesis/efectos de los fármacos , Enfermedades Renales/genética , Intoxicación por Plomo/genética , Hepatopatías/genética , Enfermedades Profesionales/genética , Polimorfismo Genético , Porfobilinógeno Sintasa/genética , Adulto , Ácido Aminolevulínico/orina , Biomarcadores/sangre , Biomarcadores/orina , China/epidemiología , Creatinina/sangre , Estudios Transversales , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Humanos , Enfermedades Renales/sangre , Enfermedades Renales/enzimología , Enfermedades Renales/etnología , Enfermedades Renales/orina , Plomo/sangre , Plomo/orina , Intoxicación por Plomo/sangre , Intoxicación por Plomo/enzimología , Intoxicación por Plomo/etnología , Intoxicación por Plomo/orina , Hepatopatías/sangre , Hepatopatías/enzimología , Hepatopatías/etnología , Hepatopatías/orina , Masculino , Persona de Mediana Edad , Enfermedades Profesionales/sangre , Enfermedades Profesionales/enzimología , Enfermedades Profesionales/etnología , Enfermedades Profesionales/orina , Exposición Profesional , Fenotipo , Porfobilinógeno Sintasa/metabolismo , Protoporfirinas/sangre , Factores de Riesgo , Adulto JovenRESUMEN
An association between polymorphous (allelic) gene variants of phase II of enzymatic xenobiotic biotransformation (EXB) of multigene families of glutathione-S-transferase (GSTs) GSTM1*0, GSTT1*0, GSTP1*B Ile105Val, and N-acetyltransferase (NAT) NAT2*6 590G>A, NAT2*5 481C>T, as well as lung cancer in Mayak workers exposed occupationally to prolonged external γ-rays and internal α-radiation from incorporated 239Pu was studied. Analysis of the population frequency of genotypes and alleles of the studied genes in the cohort of Mayak workers revealed their compliance with the Hardy-Weinberg principle and with the corresponding frequency in the European population. The study was based on the case-control method. A case-group consisted of 49 Mayal workers with a verified diagnosis of lung cancer. The mean total absorbed dose from external γ-rays at the moment of diagnostics was 1.03 Gy; the mean total absorbed dose from internal α-radiation from incorporated 239Pu to lung was 0.35 Gy. Control consisted of 172 Mayak workers matched by the year of birth, gender, and age at the moment of employment at one of the main facilities with no lung cancer registered within the study period. No increase in the relative risk of lung cancer (odds ratio, OR) was revealed among the individuals with deletion variants of genes GSTM1*0 and GSTT1*0 (pp genotype, complete absence of gene products) as compared to the individuals with ww or wp genotype, which was determined in total for these genes (normal or partly decreased gene activity). An increase in OR of lung cancer in 1.849 times (p = 0.239) and in 2.439 times (p = 0.075) was found in the carriers with a complete absence of the product of genes GSTP1*B and NAT2*6 590G>A, correspondingly (pp genotype). A statistically significant decrease in OR of lung cancer was found in the wp genotype carriers of gene GSTP1*B (OR = 0.50, p = 0.041). Three variants of paired combinations of gene alleles were established in the carriers with a statistically significant increase in OR of lung cancer (ww GSTP1*B + pp GSTM1*0; ww GSTP1*B + pp NAT2*6 590G>A; pp GSTP1*B + pp NAT2*5 481C>T), and one combination in the carriers with a statistically significant decrease in OR of lung cancer (wp GSTP1*B and ww +wp GSTT1*0).
Asunto(s)
Arilamina N-Acetiltransferasa/genética , Gutatión-S-Transferasa pi/genética , Glutatión Transferasa/genética , Neoplasias Pulmonares/genética , Neoplasias Inducidas por Radiación/genética , Enfermedades Profesionales/genética , Polimorfismo de Nucleótido Simple , Radiación Ionizante , Xenobióticos/farmacocinética , Anciano , Partículas alfa/efectos adversos , Estudios de Casos y Controles , Femenino , Rayos gamma/efectos adversos , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Industrias , Neoplasias Pulmonares/enzimología , Neoplasias Pulmonares/metabolismo , Masculino , Fase II de la Desintoxicación Metabólica , Neoplasias Inducidas por Radiación/enzimología , Neoplasias Inducidas por Radiación/metabolismo , Enfermedades Profesionales/enzimología , Enfermedades Profesionales/metabolismo , Exposición Profesional/efectos adversos , Polimorfismo de Longitud del Fragmento de Restricción , Federación de RusiaRESUMEN
The metabolic test with antipyrine was performed, the relationship between genotypes of GSTT1 and GSTM1 polymorphisms were studied, and cotinine level was measured in 116 men chronically exposed to mercury. The individuals were divided in 4 groups depending on the diagnosis of chronic mercury intoxication. The changes in the parameters of antipyrine test were studied in linked samples (N=62, 4 year interval); in patients with chronic mercury intoxication, the disease stage was taken into account. Inhibition of antipyrine metabolism, increased frequency of combination of GSTT1(0/0)/GSTM1(+) genotypes in patients with chronic mercury intoxication, and the specificity of cytochrome P450 inhibition with mercury suggest that disease progression is related to inhibition of cytochrome P450 isoforms in the brain that catalyze regulation of endogenous substrates.
Asunto(s)
Sistema Enzimático del Citocromo P-450/metabolismo , Glutatión Transferasa/genética , Intoxicación del Sistema Nervioso por Mercurio/enzimología , Mercurio/toxicidad , Enfermedades Profesionales/enzimología , Antipirina/metabolismo , Encefalopatías/inducido químicamente , Encefalopatías/enzimología , Estudios de Asociación Genética , Genotipo , Glutatión Transferasa/metabolismo , Humanos , Masculino , Enfermedades Profesionales/inducido químicamente , Exposición Profesional , Polimorfismo GenéticoRESUMEN
Lead (Pb) body burden and toxicity may be influenced by genetic polymorphisms. The aim of this study was to investigate the influence of G177C delta-aminolevulinic acid dehydratase (ALAD) polymorphism (rs1800435) on selected Pb exposure biomarkers in a population of workers highly exposed to this metal in the past. A cross-sectional survey was conducted between 2007 and 2009 within the cohort of ex-employees of a smelter in the north of France that closed down in 2003. A questionnaire was completed by each participant and blood samples enabled determination of Pb levels and ALAD polymorphism. Five parameters estimating the Pb body burden and its variations were studied: last blood lead level (BLL) during activity, cumulative blood Pb index, BLL at the time of the study, and absolute and percent changes in BLL after cessation of metal exposure. Multiple regression models were used to evaluate links between ALAD polymorphism and the selected Pb exposure biomarkers. Two hundred and four men were included. At the time of inclusion, the median age was 53.5 yr. The median duration of Pb exposure was 25 yr and the median latency since end of exposure was 5.6 yr. The frequency of ALAD-2 allele was 9.3%, with 34 subjects being heterozygous (ALAD1-2) and 2 homozygous (ALAD2-2). According to genotype, there was no significant difference for any of the five selected Pb exposure biomarkers. These results lend support to the notion that ALAD polymorphism exerts no marked impact on Pb body burden.
Asunto(s)
Predisposición Genética a la Enfermedad , Intoxicación por Plomo/genética , Metalurgia , Enfermedades Profesionales/genética , Exposición Profesional/efectos adversos , Polimorfismo Genético , Porfobilinógeno Sintasa/genética , Biomarcadores/sangre , Carga Corporal (Radioterapia) , Estudios de Cohortes , Estudios Transversales , Humanos , Intoxicación por Plomo/sangre , Intoxicación por Plomo/enzimología , Masculino , Persona de Mediana Edad , Enfermedades Profesionales/sangre , Enfermedades Profesionales/enzimología , Porfobilinógeno Sintasa/metabolismo , Encuestas y Cuestionarios , Factores de TiempoRESUMEN
OBJECTIVE: To estimate hearing loss, neurobehavioral function, and neurotransmitter alteration induced by ethylbenzene in petrochemical workers. METHODS: From two petrochemical plants, 246 and 307 workers exposed to both ethylbenzene and noise were recruited-290 workers exposed to noise only from a power station plant and 327 office personnel as control group, respectively. Hearing and neurobehavioral functions were evaluated. Serum neurotransmitters were also determined. RESULTS: The prevalence of hearing loss was much higher in petrochemical groups than that in power station and control groups (P < 0.05). Compared with the control group, scores of neurobehavioral function reflecting learning and memory were decreased in petrochemical workers (P < 0.05), as well as acetylcholinesterase activity. Negative correlation was shown between neurobehavioral function and acetylcholinesterase. CONCLUSIONS: Ethylbenzene exposure might be associated with hearing loss, neurobehavioral function impairment, and imbalance of neurotransmitters.
Asunto(s)
Contaminantes Ocupacionales del Aire/toxicidad , Derivados del Benceno/toxicidad , Pérdida Auditiva Sensorineural/inducido químicamente , Discapacidades para el Aprendizaje/inducido químicamente , Trastornos de la Memoria/inducido químicamente , Enfermedades Profesionales/inducido químicamente , Exposición Profesional/efectos adversos , Acetilcolinesterasa/sangre , Adulto , Contaminantes Ocupacionales del Aire/análisis , Derivados del Benceno/análisis , Biomarcadores/sangre , Estudios de Casos y Controles , China , Estudios Transversales , Industria Procesadora y de Extracción , Pérdida Auditiva Provocada por Ruido/etiología , Pérdida Auditiva Sensorineural/sangre , Pérdida Auditiva Sensorineural/enzimología , Pérdida Auditiva Sensorineural/etiología , Humanos , Discapacidades para el Aprendizaje/sangre , Discapacidades para el Aprendizaje/enzimología , Masculino , Trastornos de la Memoria/sangre , Trastornos de la Memoria/enzimología , Pruebas Neuropsicológicas , Neurotransmisores/sangre , Ruido en el Ambiente de Trabajo/efectos adversos , Enfermedades Profesionales/sangre , Enfermedades Profesionales/enzimología , Enfermedades Profesionales/etiología , Exposición Profesional/análisis , Oportunidad Relativa , PetróleoRESUMEN
Studies of metabolic processes in petrochemical production workers revealed activation of lipid peroxidation, depressed antioxidant system, altered intracellular metabolism, high prevalence of dyslipidemia and increased serum enzymes levels. The metabolic changes of cellular and subcellular levels were seen in asymptomatic individuals--that supports value of laboratory tests in diagnosis of pathologic processes in petrochemical production workers.
Asunto(s)
Industria Química , Pruebas Hematológicas , Enfermedades Profesionales/metabolismo , Exposición Profesional/efectos adversos , Petróleo/efectos adversos , Adulto , Biomarcadores/metabolismo , Diagnóstico Precoz , Humanos , Masculino , Concentración Máxima Admisible , Enfermedades Profesionales/enzimología , Enfermedades Profesionales/etiología , Federación de Rusia , Recursos HumanosRESUMEN
Lead is a renal toxin, and susceptibility to lead varies between individuals. Metallothionein (MT) is known for its metal scavenging role. The aim of the study was to investigate the association of blood lead levels, urinary uric acid (UA) and N-acetyl-beta-d-glucosaminidase (NAG) in chronic occupational lead-exposed workers, and to study whether the association was influenced by MT1A gene polymorphisms. In this cross-sectional study, 412 lead-exposed workers participated. Their annual health examination data and renal function markers were collected after the Institutional Review Broad of Kaohsiung Medical University Hospital approved the study and consent letters were obtained. From the blood samples, DNA was extracted and used for real-time PCR typing of 2 MT1A single nucleotide polymorphisms (SNPs): rs11640851 and rs8052394 on exons 2 and 3. Descriptive analysis, one-way ANOVA, and multiple linear regressions were performed. There was a significant inverted relationship of creatinine-adjusted urine UA concentrations and the time-weighted index of cumulative blood lead levels (TWICL) that may be significantly influenced by the AC genotypes of rs11640851 in exon 2 and rs8052394 in exon 3. After controlling for potential confounding factors, the creatinine-adjusted urine NAG concentrations were shown to be influenced by the GG genotype of rs8052394 in exon 3, and were weakly increased with TWICL. Therefore, we concluded that the variations of MT1A SNPs may influence urine UA and NAG excretion in chronic lead-exposed workers, and urine creatinine-adjusted urine UA as a biomarker of lead toxicity should be considered.
Asunto(s)
Acetilglucosaminidasa/orina , Intoxicación por Plomo/orina , Metalotioneína/genética , Metalotioneína/metabolismo , Enfermedades Profesionales/orina , Exposición Profesional/efectos adversos , Ácido Úrico/orina , Adulto , Alelos , Biomarcadores/orina , Estudios Transversales , ADN/química , ADN/genética , Femenino , Genotipo , Humanos , Intoxicación por Plomo/enzimología , Intoxicación por Plomo/genética , Modelos Lineales , Masculino , Enfermedades Profesionales/inducido químicamente , Enfermedades Profesionales/enzimología , Enfermedades Profesionales/genética , Reacción en Cadena de la Polimerasa , Polimorfismo de Nucleótido Simple , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
The ophthalmologic investigation of workers of the two metallurgical enterprises has shown that 1045 persons (55%) from 1911 observed workers suffer chronic diseases of a forward piece of eyes. Chronic inflammatory diseases (blepharitis, conjunctivitis and blepharoconjunctivitis) are found at 28,9% of them, and dystrophic diseases (pinguecula/pterygium)--at 25,8%. Among metallurgists (1801 persons) ophthalmopathy was found in 2, 2 times more often than at persons in control group (110 observed engineers and managers). Two polymorphisms of cytochrome P450 1A1 (CYP1A1) and P-450 2E1 (CYP2E1) genes were defined in 91 workers, by the method of allele-specific polymerase chain reaction. It is revealed that CYP1A1 Ile462Val polymorphism associates with pinguecula/pterygium, raising risk of their development almost in 3 times, unlike CYP 2E1 -1293G/C polymorphism. Development of chronic inflammatory diseases is not connected with tested polymorphisms.
Asunto(s)
Enfermedades de la Conjuntiva/etiología , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP2E1/genética , Enfermedades de los Párpados/etiología , Metalurgia , Enfermedades Profesionales/etiología , Polimorfismo de Nucleótido Simple , Adulto , Enfermedad Crónica , Enfermedades de la Conjuntiva/enzimología , Enfermedades de la Conjuntiva/epidemiología , Enfermedades de la Conjuntiva/genética , Enfermedades de los Párpados/enzimología , Enfermedades de los Párpados/epidemiología , Enfermedades de los Párpados/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Profesionales/enzimología , Enfermedades Profesionales/epidemiología , Enfermedades Profesionales/genética , Exposición Profesional/prevención & control , Prevalencia , Federación de RusiaRESUMEN
AIM: It is well known that polycyclic aromatic hydrocarbons (PAHs) such as benzo (a) pyrene have carcinogenic properties and may cause many types of cancers in human populations. Genetic susceptibility might be due to variation in genes encoding for carcinogen metabolizing enzymes, such as cytochrome P-450 (CYP450). Our study aimed to investigate the effect of genetic polymorphisms of CYP1A1 (m1 and m2) on genetic damage in 115 coal-tar workers exposed to PAHs in their work place. METHODS: Genetic polymorphisms of CYP1A1 were determined by the PCR-RFLP method. Comet and buccal micronucleus assays were used to evaluate genetic damage among 115 coal tar workers and 105 control subjects. RESULTS: Both CYP1A1 m1 and CYP1A1 m2 heterozygous and homozygous (wt/mt+mt/mt) variants individually as well as synergistically showed significant association (P<0.05) with genetic damage as measured by tail moment (TM) and buccal micronuclei (BMN) frequencies in control and exposed subjects. CONCLUSION: In our study we found significant association of CYP1A1 m1 and m2 heterozygous (wt/mt) +homozygous (mt/mt) variants with genetic damage suggesting that these polymorphisms may modulate the effects of PAH exposure in occupational settings.
Asunto(s)
Alquitrán/envenenamiento , Citocromo P-450 CYP1A1/genética , Daño del ADN , Neoplasias/inducido químicamente , Neoplasias/genética , Enfermedades Profesionales/inducido químicamente , Enfermedades Profesionales/genética , Exposición Profesional/efectos adversos , Adulto , Benzo(a)pireno/envenenamiento , Industria Química , Células Epiteliales/metabolismo , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Pruebas de Micronúcleos/métodos , Neoplasias/enzimología , Enfermedades Profesionales/enzimología , Hidrocarburos Policíclicos Aromáticos/envenenamiento , Polimorfismo Genético , Lugar de TrabajoRESUMEN
Styrene is a widely used chemical in the manufacture of synthetic rubber, resins, polyesters, and plastics. The highest levels of human exposure to styrene occur during the production of reinforced plastic products. The objective of this study was to examine occupational exposure to styrene in a multistage approach, in order to integrate the following endpoints: styrene in workplace air, mandelic and phenylglyoxylic acids (MA + PGA) in urine, sister chromatid exchanges (SCE), micronuclei (MN), DNA damage (comet assay), and genetic polymorphisms of metabolizing enzymes (CYP2E1, EPHX1, GSTM1, GSTT1, and GSTP1). Seventy-five workers from a fiberglass-reinforced plastics factory and 77 unexposed controls took part in the study. The mean air concentration of styrene in the breathing zone of workers (30.4 ppm) and the mean concentration of urinary metabolites (MA + PGA = 443 ± 44 mg/g creatinine) exceeded the threshold limit value (TLV) and the biological exposure index (BEI). Significantly higher SCE frequency rate and DNA damage were observed in exposed workers, but MN frequency was not markedly modified by exposure. With respect to the effect of genetic polymorphisms on different exposure and effect biomarkers studied, an increase in SCE levels with elevated microsomal epoxide hydrolase activity was noted in exposed workers, suggesting a possible exposure-genotype interaction.
Asunto(s)
Daño del ADN , Epóxido Hidrolasas/genética , Enfermedades Profesionales/inducido químicamente , Enfermedades Profesionales/genética , Exposición Profesional , Polimorfismo Genético , Estireno/toxicidad , Adolescente , Adulto , Contaminantes Ocupacionales del Aire/análisis , Contaminantes Ocupacionales del Aire/toxicidad , Biomarcadores/orina , Epóxido Hidrolasas/metabolismo , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Glioxilatos/orina , Humanos , Industrias , Masculino , Ácidos Mandélicos/orina , Persona de Mediana Edad , Mutágenos/administración & dosificación , Mutágenos/análisis , Mutágenos/toxicidad , Enfermedades Profesionales/enzimología , Enfermedades Profesionales/orina , Portugal , Intercambio de Cromátides Hermanas/efectos de los fármacos , Estireno/administración & dosificación , Estireno/análisis , Lugar de Trabajo , Adulto JovenRESUMEN
OBJECTIVES/HYPOTHESIS: The existence of nasal mucosa remodeling in allergic rhinitis is controversial. Few data are available on the dynamics of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in nasal fluid after an allergen challenge. We examined whether an immediate allergic reaction that induces nasal congestion and inflammation is able to also induce changes in remodeling parameters in nasal fluid. STUDY DESIGN: Controlled experimental study. METHODS: Ten patients with allergic occupational rhinitis due to flour underwent a control and active inhalation challenge with serial monitoring of nasal congestion and nasal symptoms with acoustic rhinometry and a visual analogue scale. Levels of remodeling markers (MMP-2, MMP-7, MMP-9, MMP-13, TIMP-1, TIMP-2) and inflammatory cells in nasal fluid were measured before the challenge and at 30 minutes, 6 hours, and 24 hours following the challenge. RESULTS: In contrast to the control challenge, the flour challenge induced nasal symptoms and significant decreases in nasal volume in all subjects. After the flour challenge, a significant increase in nasal levels of TIMP-2 and a nonsignificant increase in TIMP-1 levels were observed, whereas no significant changes in nasal levels of MMPs were documented. CONCLUSIONS: This study showed that after an inhalation challenge with an occupational allergen, the nasal mucosa displayed an imbalance in favor of TIMPs enzymes activity as compared to MMPs enzymes activity, represented in an increase in nasal levels of TIMP-2 during the course of the early reaction following the allergen challenge.
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Contaminantes Ocupacionales del Aire/efectos adversos , Harina/efectos adversos , Líquido del Lavado Nasal/química , Rinitis Alérgica Perenne/enzimología , Inhibidores Tisulares de Metaloproteinasas/metabolismo , Adulto , Contaminantes Atmosféricos , Contaminantes Ocupacionales del Aire/inmunología , Estudios de Seguimiento , Humanos , Masculino , Mucosa Nasal/enzimología , Mucosa Nasal/inmunología , Enfermedades Profesionales/diagnóstico , Enfermedades Profesionales/enzimología , Enfermedades Profesionales/inmunología , Rinitis Alérgica Perenne/diagnóstico , Rinitis Alérgica Perenne/inmunología , Rinometría AcústicaRESUMEN
BACKGROUND: Overexposure to carbon disulfide (CS(2) ) has been associated with an increase in coronary heart disease, but the mechanisms mediating this effect remain unclear. We aimed to examine the relationship between CS(2) exposure and oxidative stress markers, in order to clarify the oxidative mechanisms involved in CS(2) -induced atherosclerosis. METHODS: A total of 89 workers from a viscose rayon plant were recruited for this study, and 111 workers not exposed to CS(2) served as controls. Cholesterol, triglyceride, malondialdehyde (MDA), superoxide dismutase (SOD), catalase, GSH peroxidase, as well as total antioxidants were analyzed. RESULTS: The workers exposed to CS(2) had significantly higher MDA levels and lower SOD levels than the controls. The average MDA levels were 776 ± 268.2 (240-1,220) in the high exposure (≥10 ppm; n = 38), 751.6 ± 274 (170-1,320) in the low exposure (<10 ppm; n = 51), and 550.4 ± 199 (115-1,050) mM in the control group (n = 111). The average SOD levels were 36.5 ± 38.8 (0-223.5), 39.3 ± 38.8 (0-160), and 58.8 ± 60.8 (5.25, 400) U/ml in the high exposure-, low exposure-, and control group, respectively. MDA level increased significantly at a cumulative CS(2) exposure of over 60 ppm-years. Dyslipoproteinemia was borderline significantly associated with CS(2) exposure and MDA level. CONCLUSIONS: These results indicate that CS(2) exposure can induce oxidative stress as well as reduce the levels of antioxidative enzymes, and that a cumulative exposure level of 60 ppm-years may be a threshold value for the oxidative and the antioxidant response. Am. J. Ind. Med. 54:637-645, 2011. © 2011 Wiley-Liss, Inc.
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Contaminantes Ocupacionales del Aire/toxicidad , Aterosclerosis/inducido químicamente , Disulfuro de Carbono/toxicidad , Enfermedades Profesionales/inducido químicamente , Exposición Profesional/efectos adversos , Estrés Oxidativo , Adulto , Antioxidantes/análisis , Aterosclerosis/sangre , Aterosclerosis/enzimología , Biomarcadores/sangre , Catalasa/sangre , Celulosa , Colesterol/sangre , Estudios Transversales , Femenino , Glutatión Peroxidasa/sangre , Humanos , Masculino , Malondialdehído/sangre , Persona de Mediana Edad , Enfermedades Profesionales/sangre , Enfermedades Profesionales/enzimología , Superóxido Dismutasa/sangre , Taiwán , Textiles , Triglicéridos/sangreRESUMEN
This study elucidates the association of acrylamide metabolites, N-acetyl-S-(2-carbamoylethyl)-cysteine (AAMA), N-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-cysteine (GAMA2), and N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-cysteine (GAMA3) in urine with genetic polymorphisms of the metabolic enzymes cytochrome P450 2E1 (CYP2E1), microsomal epoxide hydrolase (mEH) in exon 3 and exon 4, glutathione transferase theta (GSTT1) and mu (GSTM1), involved in the activation and detoxification of acrylamide (AA) in humans. Eighty-five workers were recruited, including 51 AA-exposed workers and 34 administrative staffs serve as controls. Personal air sampling was performed for the exposed workers. Each subject provided pre- and post-shift urine samples and blood samples. Urinary AAMA, GAMA2 and GAMA3 levels were simultaneously quantified using liquid chromatography-electronspray ionization/tandem mass spectrometry (LC-ESI-MS/MS). CYP2E1, mEH (in exon 3 and exon 4), GSTT1, and GSTM1 were analyzed using polymerase chain reaction (PCR). Our results reveal that AA personal exposures ranged from 4.37 × 10⻳ to 113.61 µg/m³ with a mean at 15.36 µg/m³. The AAMA, GAMA2, and GAMA3 levels in the exposed group significantly exceeded those in controls. The GAMAs (the sum of GAMA2 and GAMA3)/AAMA ratios, potentially reflecting the proportion of AA metabolized to glycidamide (GA), varied from 0.003 to 0.456, and indicate high inter-individual variability in the metabolism of AA to GA in this study population. Multivariate regression analysis demonstrates that GSTM1 genotypes significantly modify the excretion of urinary AAMA and the GAMAs/AAMA ratio, exon 4 of mEH was significantly associated with the urinary GAMAs levels after adjustment for AA exposures. These results suggest that mEH and/or GSTM1 may be associated with the formation of urinary AAMA and GAMAs. Further study may be needed to shed light on the role of both enzymes in AA metabolism.
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Acrilamida/envenenamiento , Citocromo P-450 CYP2E1/genética , Epóxido Hidrolasas/genética , Glutatión Transferasa/genética , Enfermedades Profesionales/inducido químicamente , Exposición Profesional/efectos adversos , Acrilamida/orina , Adulto , Citocromo P-450 CYP2E1/metabolismo , ADN/química , ADN/genética , Epóxido Hidrolasas/metabolismo , Femenino , Genotipo , Glutatión Transferasa/metabolismo , Humanos , Masculino , Análisis Multivariante , Enfermedades Profesionales/enzimología , Enfermedades Profesionales/orina , Reacción en Cadena de la Polimerasa , Polimorfismo Genético , Análisis de RegresiónRESUMEN
There is a wide variation in sensitivity to lead (Pb) exposure, which may be due to genetic susceptibility towards Pb. We investigated whether a polymorphism (rs1800435) in the δ-aminolevulinic acid dehydratase (ALAD) gene affected the toxicokinetics and toxicodynamics of Pb. Among 461 Chinese Pb-exposed storage battery and 175 unexposed workers, allele frequencies for the ALAD1 and ALAD2 alleles were 0.968 and 0.032, respectively. The Pb-exposed workers had a higher fraction of the ALAD1-2/2-2 genotype than unexposed workers (7.8% vs. 2.3%, p=0.01). The Pb levels in blood (B-Pb) and urine (U-Pb) were higher in Pb-exposed workers carrying the ALAD2 allele compared to homozygotes for ALAD1 (median B-Pb: 606 vs. 499 µg/L; U-Pb: 233 vs. 164 µg/g creatinine), while there was no statistically significant difference in the unexposed controls (median: 24 vs. 37 µg/L, and 3.9 vs. 6.4µg/g creatinine, respectively). High B-Pb and U-Pb were associated with statistically significantly lower sensory and motor conduction velocities in the median, ulnar and peroneal nerves. At the same B-Pb and U-Pb, ALAD1 homozygotes had lower conduction velocities than the ALAD2 carriers. There were similar trends for toxic effects on haem synthesis (zinc protoporphyrin and haemoglobin in blood) and renal function (albumin and N-acetyl-d-ß-acetylglucosaminidase in urine), but without statistical significance. There was no difference in Pb toxicokinetics and toxicodynamics associated with VDR BsmI polymorphism. Our results show that the ALAD genotype modifies the relationship between Pb and its toxic effects on the peripheral nervous system. This must be considered in the assessment of risks at Pb exposure.
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Suministros de Energía Eléctrica/efectos adversos , Intoxicación del Sistema Nervioso por Plomo en Adultos/genética , Plomo/efectos adversos , Neuropatía Mediana/genética , Enfermedades Profesionales/genética , Exposición Profesional , Neuropatías Peroneas/genética , Polimorfismo Genético , Porfobilinógeno Sintasa/genética , Neuropatías Cubitales/genética , Adolescente , Adulto , Estudios de Casos y Controles , China , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Hemo/biosíntesis , Homocigoto , Humanos , Riñón/metabolismo , Riñón/fisiopatología , Plomo/sangre , Plomo/orina , Intoxicación del Sistema Nervioso por Plomo en Adultos/enzimología , Intoxicación del Sistema Nervioso por Plomo en Adultos/fisiopatología , Modelos Lineales , Masculino , Neuropatía Mediana/inducido químicamente , Neuropatía Mediana/enzimología , Neuropatía Mediana/fisiopatología , Persona de Mediana Edad , Conducción Nerviosa/efectos de los fármacos , Examen Neurológico , Enfermedades Profesionales/enzimología , Enfermedades Profesionales/fisiopatología , Neuropatías Peroneas/inducido químicamente , Neuropatías Peroneas/enzimología , Neuropatías Peroneas/fisiopatología , Fenotipo , Porfobilinógeno Sintasa/metabolismo , Receptores de Calcitriol/genética , Medición de Riesgo , Factores de Riesgo , Sensación/efectos de los fármacos , Neuropatías Cubitales/inducido químicamente , Neuropatías Cubitales/enzimología , Neuropatías Cubitales/fisiopatología , Adulto JovenRESUMEN
The authors represent results of studies concerning distribution of CPOX and TNF-alpha genes in workers engaged into chemical production. Findings are peculiarities of genetic polymorphism of CPOX gene and TNF gene, and their association with biologic media contamination with methylated phenols (m-cresol) and apoptosis disorders.
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Coproporfirinógeno Oxidasa/genética , Enfermedades Profesionales/genética , Exposición Profesional/efectos adversos , Polimorfismo Genético , Factor de Necrosis Tumoral alfa/genética , Adulto , Apoptosis/genética , Industria Química , Cresoles/toxicidad , Humanos , Persona de Mediana Edad , Enfermedades Profesionales/inducido químicamente , Enfermedades Profesionales/enzimología , Adulto JovenRESUMEN
The paper gives the basic results of studying the polymorphic loci of the genes of xenobiotic transformation enzymes, antioxidative defense, and DNA repair in petrochemical workers. Polymerase chain reaction-restriction fragment length polymorphism assay was used to identify markers of the predisposition to the development of toxic hepatitis in men and impaired reproduction in women.