RESUMEN
Urinary mutagenicity reflects systemic exposure to complex mixtures of genotoxic/carcinogenic agents and is linked to tumor development. Coal combustion emissions (CCE) and diesel engine exhaust (DEE) are associated with cancers of the lung and other sites, but their influence on urinary mutagenicity is unclear. We investigated associations between exposure to CCE or DEE and urinary mutagenicity. In two separate cross-sectional studies of nonsmokers, organic extracts of urine were evaluated for mutagenicity levels using strain YG1041 in the Salmonella (Ames) mutagenicity assay. First, we compared levels among 10 female bituminous (smoky) coal users from Laibin, Xuanwei, China, and 10 female anthracite (smokeless) coal users. We estimated exposure-response relationships using indoor air concentrations of two carcinogens in CCE relevant to lung cancer, 5-methylchrysene (5MC), and benzo[a]pyrene (B[a]P). Second, we compared levels among 20 highly exposed male diesel factory workers and 15 unexposed male controls; we evaluated exposure-response relationships using elemental carbon (EC) as a DEE-surrogate. Age-adjusted linear regression was used to estimate associations. Laibin smoky coal users had significantly higher average urinary mutagenicity levels compared to smokeless coal users (28.4 ± 14.0 SD vs. 0.9 ± 2.8 SD rev/ml-eq, p = 2 × 10-5 ) and a significant exposure-response relationship with 5MC (p = 7 × 10-4 ). DEE-exposed workers had significantly higher urinary mutagenicity levels compared to unexposed controls (13.0 ± 10.1 SD vs. 5.6 ± 4.4 SD rev/ml-eq, p = .02) and a significant exposure-response relationship with EC (p-trend = 2 × 10-3 ). Exposure to CCE and DEE is associated with urinary mutagenicity, suggesting systemic exposure to mutagens, potentially contributing to cancer risk and development at various sites.
Asunto(s)
Contaminantes Ocupacionales del Aire/orina , Carbón Mineral/efectos adversos , Mutágenos/análisis , Enfermedades Profesionales/epidemiología , Exposición Profesional/efectos adversos , Fumar/orina , Emisiones de Vehículos/análisis , Contaminantes Ocupacionales del Aire/efectos adversos , China/epidemiología , Carbón Mineral/análisis , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutágenos/efectos adversos , Enfermedades Profesionales/diagnóstico , Enfermedades Profesionales/genética , Enfermedades Profesionales/orina , Exposición Profesional/análisis , Fumar/efectos adversosRESUMEN
BACKGROUND: Millions of people are at risk from the adverse effects of arsenic exposure through drinking water. Increasingly, non-cancer effects such as cardiovascular disease have been associated with drinking water arsenic exposures. However, most studies have been conducted in highly exposed populations and lacked individual measurements. OBJECTIVE: To evaluate the association between cardiovascular disease and well-water arsenic exposure. METHODS: We conducted a hospital based case control study in Inner Mongolia, China. Cases and controls were prospectively identified and enrolled from a large hospital in the Hangjin Hou area. Cases were patients diagnosed with cardiovascular disease and controls were patients free from cardiovascular disease, admitted for conditions unrelated to arsenic exposure. Water from the primary water source and toenail samples were collected from each subject and tested for inorganic arsenic. RESULTS: Arsenic exposures were moderate with mean and median arsenic exposures of 8.9 µg/L and 13.1 µg/L, respectively. A total of 298 cases and 275 controls were enrolled. The adjusted odds ratio (AOR) and corresponding 95% confidence interval (95% CI) for a 10 µg/L increase in water arsenic were 1.19 (95% CI: 1.03, 1.38). Compared to exposures less than 10 µg/L, the AOR for water arsenic exposures above 40 µg/L was 4.05 (95% CI: 1.1-14.99, p = 0.04). Nail arsenic above 1.38 µg/g was also associated with an increased risk of cardiovascular disease. CONCLUSIONS: By using standardized case definitions and collecting individual measurements of arsenic, this study addressed several limitations of previous studies. The results provide further evidence of the association between cardiovascular disease and arsenic at moderate exposures.
Asunto(s)
Arsénico/toxicidad , Enfermedades Cardiovasculares/epidemiología , Agua Potable/análisis , Exposición a Riesgos Ambientales , Contaminantes Químicos del Agua/toxicidad , Adolescente , Adulto , Anciano , Enfermedades Cardiovasculares/inducido químicamente , Estudios de Casos y Controles , China/epidemiología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Pozos de Agua , Adulto JovenRESUMEN
Chronic arsenic exposure results in higher risk of skin, lung, and bladder cancer, as well as cardiovascular disease and diabetes. The purpose of this study was to investigate the effects on expression of selected genes in the blood lymphocytes from 159 people exposed chronically to arsenic in their drinking water using a novel RT-PCR TaqMan low-density array (TLDA). We found that expression of tumor necrosis factor-α (TNF-α), which activates both inflammation and NF-κB-dependent survival pathways, was strongly associated with water and urinary arsenic levels. Expression of KCNA5, which encodes a potassium ion channel protein, was positively associated with water and toe nail arsenic levels. Expression of 2 and 11 genes were positively associated with nail and urinary arsenic, respectively. Because arsenic exposure has been reported to be associated with long QT intervals and vascular disease in humans, we also used this TLDA for analysis of gene expression in human cardiomyocytes exposed to arsenic in vitro. Expression of the ion-channel genes CACNA1, KCNH2, KCNQ1 and KCNE1 were down-regulated by 1-µM arsenic. Alteration of some common pathways, including those involved in oxidative stress, inflammatory signaling, and ion-channel function, may underlay the seemingly disparate array of arsenic-associated diseases, such as cancer, cardiovascular disease, and diabetes.
Asunto(s)
Arsénico/administración & dosificación , Arsénico/metabolismo , Expresión Génica/efectos de los fármacos , Miocitos Cardíacos/efectos de los fármacos , Reacción en Cadena en Tiempo Real de la Polimerasa , Adolescente , Adulto , Niño , Relación Dosis-Respuesta a Droga , Exposición a Riesgos Ambientales , Femenino , Humanos , Canales Iónicos/metabolismo , Linfocitos/efectos de los fármacos , Masculino , Persona de Mediana Edad , Miocitos Cardíacos/metabolismo , Manejo de Especímenes , Encuestas y Cuestionarios , Adulto JovenRESUMEN
The skin is an organ that is highly sensitive to chronic arsenic (As) exposure. Skin lesions such as hyperkeratoses (HKs) are common early manifestations of arsenicosis in humans. HKs can be precursor lesions of nonmelanoma skin cancers (NMSCs), but the driving forces behind their formation and how they may ultimately progress to NMSCs are unknown. The goal of this study was to examine the global gene expression profiles of As-related HKs in an effort to better understand gene expression changes that are potentially associated with early stages of As carcinogenesis. HK biopsies were removed from individuals living in an arsenicosis-endemic region in Inner Mongolia who had been exposed to high As levels in their drinking water for >20 years. Gene expression profiling was performed on RNA isolated from 7 individuals in this group and from 4 lesion-free skin samples from healthy individuals. Consistent with the pathological characteristics of the HK lesions, major functional categories and known canonical pathways represented by altered transcripts include those involved in development, differentiation, apoptosis, proliferation, and stress response. The results of this study may help define a signature profile of gene expression changes associated with long-term As exposure in the skin.
Asunto(s)
Intoxicación por Arsénico/genética , Regulación de la Expresión Génica/efectos de los fármacos , Queratosis/inducido químicamente , Queratosis/genética , Adulto , Apoptosis/efectos de los fármacos , Apoptosis/genética , Arsénico/toxicidad , Intoxicación por Arsénico/patología , Señalización del Calcio/efectos de los fármacos , Señalización del Calcio/genética , Carcinógenos/toxicidad , Adhesión Celular/efectos de los fármacos , Adhesión Celular/genética , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/genética , Proliferación Celular/efectos de los fármacos , China , Citoesqueleto/efectos de los fármacos , Citoesqueleto/genética , Daño del ADN/efectos de los fármacos , Daño del ADN/genética , Reparación del ADN/efectos de los fármacos , Reparación del ADN/genética , Femenino , Perfilación de la Expresión Génica , Humanos , Queratosis/patología , Masculino , Persona de Mediana Edad , Proteínas Quinasas Activadas por Mitógenos/genética , Neoplasias Cutáneas/inducido químicamente , Estrés Fisiológico/efectos de los fármacos , Estrés Fisiológico/genética , Proteína Wnt1/genética , beta Catenina/genéticaRESUMEN
BACKGROUND: Chronic arsenic exposure has been associated with human cancer. The objective of this study was to investigate the effects of arsenic exposure on a DNA nucleotide excision repair gene, ERCC1, expression in human blood cells. PATIENTS AND METHODS: Water and toenail samples were collected from a total of 327 Inner Mongolian residents for arsenic analysis. Blood samples were collected to determine mRNA expression levels by real-time PCR. RESULTS: The mRNA levels of ERCC1 expression were positively associated with water arsenic concentration (slope=0.313, p=0.0043) and nail arsenic concentration (slope=0.474, p=0.0073). mRNA levels of ERCC1 expression were significantly correlated with those of OGG1, a base pair excision repair gene (r=0.275, p<0.0001). CONCLUSION: The results showed that mRNA levels of ERCC1 expression were significantly associated with arsenic concentrations in drinking water, implicating the DNA repair response was induced by arsenic exposure.
Asunto(s)
Intoxicación por Arsénico/genética , Arsénico/análisis , Células Sanguíneas/química , Proteínas de Unión al ADN/genética , Endonucleasas/genética , Exposición a Riesgos Ambientales/análisis , Contaminantes Químicos del Agua , Abastecimiento de Agua/análisis , Adolescente , Adulto , Células Sanguíneas/metabolismo , Niño , China , ADN Glicosilasas/genética , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Uñas/química , Pronóstico , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Adulto JovenRESUMEN
Residents of the Bayingnormen region of Inner Mongolia have been exposed to arsenic-contaminated well water for over 20 years, but relatively few studies have investigated health effects in this region. We surveyed one village to document exposure to arsenic and assess the prevalence of arsenic-associated skin lesions and self-reported morbidity. Five-percent (632) of the 12,334 residents surveyed had skin lesions characteristics of arsenic exposure. Skin lesions were strongly associated with well water arsenic and there was an elevated prevalence among residents with water arsenic exposures as low as 5 microg/L-10 microg/L. The presence of skin lesions was also associated with self-reported cardiovascular disease.
Asunto(s)
Intoxicación por Arsénico/epidemiología , Exposición a Riesgos Ambientales , Enfermedades de la Piel/inducido químicamente , Contaminantes Químicos del Agua/toxicidad , Contaminación Química del Agua/efectos adversos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , China/epidemiología , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Vigilancia de la Población , Prevalencia , Enfermedades de la Piel/epidemiología , Contaminación Química del Agua/análisis , Adulto JovenRESUMEN
We conducted a retrospective mortality study in an Inner Mongolian village exposed to well water contaminated by arsenic since the 1980s. Deaths occurring between January 1, 1997 and December 1, 2004 were classified according to underlying cause and water samples from household wells were tested for total arsenic. Heart disease mortality was associated with arsenic exposure, and the association strengthened with time exposed to the water source. Cancer mortality and all-cause mortality were associated with well-water arsenic exposure among those exposed 10-20 years. This is the first study to document increased arsenic-associated mortality in the Bayingnormen region of Inner Mongolia.
Asunto(s)
Intoxicación por Arsénico/mortalidad , Arsénico/toxicidad , Causas de Muerte , Exposición a Riesgos Ambientales , Contaminantes Químicos del Agua/toxicidad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Arsénico/análisis , Niño , Preescolar , China/epidemiología , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Contaminantes Químicos del Agua/análisis , Adulto JovenRESUMEN
BACKGROUND: Arsenic exposure is associated with human cancer. Telomerase-containing human telomerase reverse transcriptase (hTERT) can extend telomeres of chromosomes, delay senescence, and promote cell proliferation leading to tumorigenesis. OBJECTIVE: The goal of this study was to investigate the effects of As on hTERT mRNA expression in humans and in vitro. METHOD: A total of 324 Inner Mongolia residents who have been exposed to As via drinking water participated in this study. Water and toenail samples were collected and analyzed for As. Blood samples were quantified for hTERT mRNA expression using real-time polymerase chain reaction. The hTERT mRNA levels were linked to water and nail As concentrations and skin hyperkeratosis. Human epidermal keratinocytes were treated with arsenite to assess effects on cell viability and hTERT expression in vitro. RESULTS: hTERT mRNA expression levels were significantly associated with As concentrations of water (p<0.0001) and nails (p=0.002) and also associated with severity of skin hyperkeratosis (p<0.05), adjusting for age, sex, smoking, and pesticide use. Females showed a higher slope than males (females: 0.126, p=0.0005; males: 0.079, p=0.017). In addition to water and nail As concentrations, age (p<0.0001) and pesticide use (p=0.025) also showed significant associations with hTERT expression. The hTERT expression levels decreased with age. Tobacco smoking did not affect hTERT expression (p=0.13). hTERT expression was significantly correlated with OGG1 and ERCC1 expression. The in vitro results also showed a dose-response relationship between arsenite concentrations and hTERT expression and reached the peak at 1 microM. CONCLUSIONS: hTERT expression was associated with As exposure in vivo and in vitro. The increased hTERT expression may be a cellular response to genomic insults by As and may also indicate that As may function as a tumor promoter in carcinogenesis in humans.
Asunto(s)
Arsénico/toxicidad , Exposición a Riesgos Ambientales , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Telomerasa/metabolismo , Contaminantes Químicos del Agua/toxicidad , Factores de Edad , Células Sanguíneas/enzimología , China , Relación Dosis-Respuesta a Droga , Femenino , Agua Dulce/química , Humanos , Masculino , Uñas/química , Factores SexualesRESUMEN
BACKGROUND: Recent studies suggested the potential for aberrant gene promoter methylation in sputum as predictive marker for lung cancer. Here, the promoter methylation of p16, MGMT, RASSF1A and DAPK genes was investigated in sputum of individuals exposed to smoky coal emissions in Xuan Wei, China, where the lung cancer rate more than 6 times the Chinese national average. MATERIALS AND METHODS: Sputum DNA of 107 noncancer individuals and 58 lung cancer patients was screened for promoter methylation using methylation-specific PCR. RESULTS: Promoter methylation of the p16 gene was detected in about half [51.4% (55/107)] sputum DNA from noncancer individuals, a frequency higher than that observed for the RASSF1A (29.9%), MGMT (17.8%) and DAPK (15.9%) genes. Furthermore, the p16 gene was affected by promoter methylation at a frequency even higher among the lung cancer group, compared with the noncancer group [70.7% (41/58) versus 51.7% (55/107), p = 0.017]. CONCLUSION: Individuals exposed to smoky coal emissions in this region harbored frequent promoter methylation of these genes in their sputum and some of such alterations may be involved in lung tumor development.
Asunto(s)
Carbón Mineral/envenenamiento , Metilación de ADN , ADN/análisis , Neoplasias Pulmonares/etiología , Neoplasias Pulmonares/genética , Humo/efectos adversos , Esputo/fisiología , Proteínas Reguladoras de la Apoptosis/genética , Bronquitis/etiología , Bronquitis/genética , Proteínas Quinasas Dependientes de Calcio-Calmodulina/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina , ADN/genética , Proteínas Quinasas Asociadas a Muerte Celular , Exposición a Riesgos Ambientales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/genética , Regiones Promotoras Genéticas , Esputo/efectos de los fármacos , Proteínas Supresoras de Tumor/genéticaRESUMEN
BACKGROUND: Determination of arsenic species in saliva is potentially useful for biomonitoring of human exposure and studying arsenic metabolism. Arsenic speciation in saliva has not been reported previously. METHODS: We separated arsenic species in saliva using liquid chromatography (LC) and quantified them by inductively coupled plasma mass spectrometry. We further confirmed the identities of arsenic species by LC coupled with electrospray ionization tandem mass spectrometry. These methods were successfully applied to the determination of arsenite (As(III)), arsenate (As(V)), and their methylation metabolites, monomethylarsonic acid (MMA(V)), and dimethylarsinic acid (DMA(V)), in >300 saliva samples collected from people who were exposed to varying concentrations of arsenic. RESULTS: The mean (range) concentrations (microg/L) in the saliva samples from 32 volunteers exposed to background levels of arsenic were As(III) 0.3 [not detectable (ND) to 0.7], As(V) 0.3 (ND to 0.5), MMA(V) 0.1 (ND to 0.2), and DMA(V) 0.7 (ND to 2.6). Samples from 301 people exposed to increased concentrations of arsenic in drinking water showed detectable As(III) in 99%, As(V) in 98%, MMA(V) in 80%, and DMA(V) in 68% of samples. The mean (range) concentrations of arsenic species in these saliva samples were (in microg/L) As(III) 2.8 (0.1-38), As(V) 8.1 (0.3-120), MMA(V) 0.8 (0.1-6.0), and DMA(V) 0.4 (0.1-3.9). Saliva arsenic correlated with drinking water arsenic. Odds ratios for skin lesions increased with saliva arsenic concentrations. The association between saliva arsenic concentrations and the prevalence of skin lesions was statistically significant (P <0.001). CONCLUSIONS: Speciation of As(V), As(III), MMA(V), and DMA(V) in human saliva is a useful method for monitoring arsenic exposure.
Asunto(s)
Arsenicales/análisis , Saliva/química , Adulto , Arseniatos/análisis , Arseniatos/toxicidad , Intoxicación por Arsénico/etiología , Arsenitos/análisis , Arsenitos/toxicidad , Ácido Cacodílico/análisis , Ácido Cacodílico/toxicidad , Cromatografía Liquida , Exposición a Riesgos Ambientales/efectos adversos , Femenino , Agua Dulce/química , Humanos , Masculino , Espectrometría de Masas/métodos , Persona de Mediana Edad , Estándares de Referencia , Enfermedades de la Piel/inducido químicamenteRESUMEN
BACKGROUND: Chronic arsenic exposure is associated with cardiovascular abnormalities. Prolongation of the QT (time between initial deflection of QRS complex to the end of T wave) interval and profound repolarization changes on electrocardiogram (ECG) have been reported in patients with acute promyelocytic leukemia treated with arsenic trioxide. This acquired form of long QT syndrome can result in life-threatening arrhythmias. OBJECTIVE: The objective of this study was to assess the cardiac effects of arsenic by investigating QT interval alterations in a human population chronically exposed to arsenic. METHODS: Residents in Ba Men, Inner Mongolia, have been chronically exposed to arsenic via consumption of water from artesian wells. A total of 313 Ba Men residents with the mean arsenic exposure of 15 years were divided into three arsenic exposure groups: low (< or = 21 microg/L), medium (100-300 microg/L), and high (430-690 microg/L). ECGs were obtained on all study subjects. The normal range for QTc (corrected QT) interval is 0.33-0.44 sec, and QTc > or = 0.45 sec was considered to be prolonged. RESULTS: The prevalence rates of QT prolongation and water arsenic concentrations showed a dose-dependent relationship (p = 0.001). The prevalence rates of QTc prolongation were 3.9, 11.1, 20.6% for low, medium, and high arsenic exposure, respectively. QTc prolongation was also associated with sex (p < 0.0001) but not age (p = 0.486) or smoking (p = 0.1018). Females were more susceptible to QT prolongation than males. CONCLUSIONS: We found significant association between chronic arsenic exposure and QT interval prolongation in a human population. QT interval may potentially be useful in the detection of early cardiac arsenic toxicity.
Asunto(s)
Arsénico/toxicidad , Anomalías Cardiovasculares/epidemiología , Exposición a Riesgos Ambientales , Sístole/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , Adulto , Arsénico/análisis , Anomalías Cardiovasculares/inducido químicamente , China/epidemiología , Electrocardiografía/métodos , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Funciones de Verosimilitud , Modelos Logísticos , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Contaminantes Químicos del Agua/análisisRESUMEN
The extremely high exposure levels evaluated in prior investigations relating elevated levels of drinking water arsenic and hypertension prevalence make extrapolation to potential vascular effects at lower exposure levels very difficult. A cross-sectional study was conducted on 8790 women who had recently been pregnant in an area of Inner Mongolia, China known to have a gradient of drinking water arsenic exposure. This study observed increased systolic blood pressure levels with increasing drinking water arsenic, at lower exposure levels than previously reported in the literature. As compared to the referent category (below limit of detection to 20 microg of As/L), the overall population mean systolic blood pressure rose 1.29 mm Hg (95% CI 0.82, 1.75), 1.28 mm Hg (95% CI 0.49, 2.07), and 2.22 mm Hg (95% CI 1.46, 2.97) as drinking water arsenic concentration increased from 21 to 50, 51 to 100, and >100 microg of As/L, respectively. Controlling for age and body weight (n=3260), the population mean systolic blood pressure rose 1.88 mm Hg (95% CI 1.03, 2.73), 3.90 mm Hg (95% CI 2.52, 5.29), and 6.83 mm Hg (95% CI 5.39, 8.27) as drinking water arsenic concentration increased, respectively. For diastolic blood pressure effect, while statistically significant, was not as pronounced as systolic blood pressure. Mean diastolic blood pressure rose 0.78 mm Hg (95% CI 0.39, 1.16), 1.57 mm Hg (95% CI 0.91, 2.22) and 1.32 mm Hg (95% CI 0.70, 1.95), respectively, for the overall population and rose 2.11 mm Hg (95% CI 1.38, 2.84), 2.74 mm Hg (95% CI 1.55, 3.93), and 3.08 mm Hg (95% CI 1.84, 4.31), respectively, for the adjusted population (n=3260) at drinking water arsenic concentrations of 21 to 50, 51 to 100, and >100 microg of As/L. If our study results are confirmed in other populations, the potential burden of cardiovascular disease attributable to drinking water arsenic is significant.
Asunto(s)
Arsénico/toxicidad , Presión Sanguínea/efectos de los fármacos , Venenos/toxicidad , Abastecimiento de Agua , Adulto , Análisis de Varianza , Peso Corporal/efectos de los fármacos , China/epidemiología , Estudios Transversales , Femenino , Humanos , Embarazo , Estudios Retrospectivos , Factores de RiesgoRESUMEN
In the Ba Men region of Inner Mongolia, China, a high prevalence of chronic arsenism has been reported in earlier studies. A survey of the arsenic contamination among wells from groundwater was conducted to better understand the occurrence of arsenic (As) in drinking water. A total of 14,866 wells (30% of all wells in the region) were analyzed for their arsenic-content. Methods used to detect arsenic were Spectrophotometric methods with DCC-Ag (detection limit, 0.5 microg of As/L); Spot method (detection limit, 10 microg of As/L); and air assisted Colorimetry method (detection limit, 20 microg of As/L). Arsenic-concentrations ranged from below limit of detection to 1200 microg of As/L. Elevated concentrations were related to well depth (10 to 29 m), the date the well was built (peaks from 1980-1990), and geographic location (near mountain range). Over 25,900 individuals utilized wells with drinking water arsenic concentrations above 20 microg of As/L (14,500 above 50 microg of As/L-the current China national standard in drinking water and 2198 above 300 microg of As/L). The presented database of arsenic in wells of the Ba Men region provides a useful tool for planning future water explorations when combined with geological information as well as support for designing upcoming epidemiological studies on the effects of arsenic in drinking water for this region.
Asunto(s)
Arsénico/análisis , Venenos/análisis , Abastecimiento de Agua/análisis , China/epidemiología , Colorimetría , Geografía , Planificación en Salud , Humanos , Abastecimiento de Agua/normasRESUMEN
Arsenic, a human carcinogen, is known to induce oxidative damage to DNA. In this study we investigated oxidative stress and As exposure by determining gene expression of OGG1, which codes for an enzyme, 8-oxoguanine DNA glycosylase, involved in removing 8-oxoguanine in As-exposed individuals. Bayingnormen (Ba Men) residents in Inner Mongolia are chronically exposed to As via drinking water. Water, toenail, and blood samples were collected from 299 Ba Men residents exposed to 0.34-826 microg/L As. RNA was isolated from blood, and mRNA levels of OGG1 were determined using real-time polymerase chain reaction. OGG1 expression levels were linked to As concentrations in drinking water and nails, selenium concentrations in nails, and skin hyperkeratosis. OGG1 expression was strongly associated with water As concentrations (p < 0.0001). Addition of the quadratic term significantly improved the fit compared with the linear model (p = 0.05) . The maximal OGG1 response was at the water As concentration of 149 microg/L. OGG1 expression was also significantly associated with toenail As concentrations (p = 0.015) but inversely associated with nail Se concentrations (p = 0.0095) . We found no significant differences in the As-induced OGG1 expression due to sex, smoking, or age even though the oldest group showed the strongest OGG1 response (p = 0.0001) . OGG1 expression showed a dose-dependent increased risk of skin hyperkeratosis in males (trend analysis, p = 0.02) , but the trend was not statistically significant in females. The results from this study provide a linkage between oxidative stress and As exposure in humans. OGG1 expression may be useful as a biomarker for assessing oxidative stress from As exposure.
Asunto(s)
Arsénico/toxicidad , ADN Glicosilasas/genética , Uñas/química , Estrés Oxidativo , Selenio/análisis , Enfermedades de la Piel/inducido químicamente , Adolescente , Adulto , Niño , China , Cromatografía Líquida de Alta Presión , Femenino , Humanos , Masculino , Persona de Mediana Edad , ARN Mensajero/genéticaRESUMEN
This study was designed to assess the effects of exposure to arsenic in drinking water on visual and vibrotactile function in residents of the Bamen region of Inner Mongolia, China. Arsenic was measured by hydride generation atomic fluorescence. 321 participants were divided into three exposure groups- low (non-detectable-20), medium (100-300) and high (400-700 microg/l) arsenic in drinking water (AsW). Three visual tests were administered: acuity, contrast sensitivity and color discrimination (Lanthony's Desaturated 15 Hue Test). Vibration thresholds were measured with a vibrothesiometer. Vibration thresholds were significantly elevated in the high exposure group compared to other groups. Further analysis using a spline regression model suggested that the threshold for vibratory effects is between 150-170 microg/l AsW. These findings provide the first evidence that chronic exposure to arsenic in drinking water impairs vibrotactile thresholds. The results also indicate that arsenic affects neurological function well below the 1000 microg/I concentration reported by NRC (1999). No evidence of arsenic-related effects on visual function was found.
Asunto(s)
Arsénico/efectos adversos , Exposición a Riesgos Ambientales , Enfermedades del Sistema Nervioso/inducido químicamente , Vibración , Agudeza Visual , Abastecimiento de Agua/análisis , Adolescente , Adulto , Arsénico/sangre , Arsénico/aislamiento & purificación , Niño , China , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso/diagnóstico , Encuestas y Cuestionarios , Microbiología del Agua , Contaminantes Químicos del Agua/aislamiento & purificaciónRESUMEN
This study was designed to assess the effects of exposure to arsenic in drinking water on neurosensory function. A questionnaire including neurological signs and symptoms and a brief neurological exam consisting of pinprick testing of the arms and legs and knee-jerk test were administered to 321 residents of the Bamen region of Inner Mongolia, China. Arsenic in water was measured by hydride generation atomic fluorescence. Participants were divided into three exposure groups--low (non-detectible-20), medium (100-300) and high (400-700 microg/I) arsenic. Significant group differences were observed in pinprick scores for all four limbs. Results indicate that arsenic alters pinprick (pain) thresholds at well-water concentrations as low as 400 microg/l, well below the 1000 microg/l threshold for neurological effect specified by NRC (1999). Regression models suggest that a 50% increase in pinprick score is associated with a 71-159 ppb increase in arsenic concentration.
Asunto(s)
Arsénico/sangre , Exposición a Riesgos Ambientales , Enfermedades del Sistema Nervioso/inducido químicamente , Abastecimiento de Agua/análisis , Adulto , Arsénico/aislamiento & purificación , China , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso/diagnóstico , Encuestas y Cuestionarios , Microbiología del Agua , Contaminantes Químicos del Agua/aislamiento & purificaciónRESUMEN
The lung cancer mortality rate in Xuan Wei is among the highest in China and has been causally attributed to high exposure to indoor smoky coal emissions, which contain high levels of PAHs and can lead to modified bases. We studied genetic polymorphisms in four DNA base excision repair genes in a population-based case-control study in Xuan Wei with 122 lung cancer cases and 122 controls. Homozygous carriers of the APEX1 148Glu variant had an increased risk (OR, 2.13; 95% CI, 0.96-4.74), whereas persons with the XRCC1 399Gln allele had a decreased risk (OR, 0.60; 95% CI, 0.35-1.02) of lung cancer compared with wild-type carriers. Subjects with both at-risk genotypes (APEX1 Glu148Glu and XRCC1 Arg399Arg) had a higher risk of lung cancer (OR: 3.34; 95% CI: 1.16-9.67). We found genetic variants in APEX1 and XRCC1 may alter the risk of lung cancer in a special population in China.
Asunto(s)
ADN-(Sitio Apurínico o Apirimidínico) Liasa/genética , Proteínas de Unión al ADN/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Polimorfismo Genético , Adulto , Anciano , China , Daño del ADN , Reparación del ADN , Femenino , Genotipo , Homocigoto , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Riesgo , Proteína 1 de Reparación por Escisión del Grupo de Complementación Cruzada de las Lesiones por Rayos XRESUMEN
The lung cancer mortality rate in Xuan Wei County is among the highest in China and has been attributed to exposure to indoor smoky coal emissions that contain very high levels of polycyclic aromatic hydrocarbons (PAHs). Nucleotide excision repair (NER) plays a key role in reversing DNA damage from exposure to environmental carcinogens, such as PAHs, that form bulky DNA adducts. We studied single nucleotide polymorphisms (SNPs) and their corresponding haplotypes in 6 genes (ERCC1, ERCC2/XPD, ERCC4/XPF, ERCC5/XPG, RAD23B and XPC) involved in NER in a population-based case-control study of lung cancer in Xuan Wei. A total of 122 incident primary lung cancer cases and 122 individually matched controls were enrolled. Three linked SNPs in ERCC2 were associated with lung cancer with similar ORs; e.g., persons with the Gln allele at codon 751 had a 60% reduction of lung cancer (OR = 0.40, 95% CI 0.18-0.89). Moreover, one haplotype in ERCC2 was associated with a decreased risk of lung cancer (OR = 0.40, 95% CI 0.19-0.85) compared to the most common haplotype. In addition, subjects with one or 2 copies of the Val allele at codon 249 of RAD23B had a 2-fold increased risk of lung cancer (OR = 1.91, 95% CI 1.12-3.24). In summary, our results suggest that genetic variants in genes involved in the NER pathway may play a role in lung cancer susceptibility in Xuan Wei. However, due to the small sample size, additional studies are needed to evaluate these associations within Xuan Wei and in other populations with substantial environmental exposure to PAHs.
Asunto(s)
Reparación del ADN/genética , Neoplasias Pulmonares/genética , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Estudios de Casos y Controles , ADN Helicasas/genética , Enzimas Reparadoras del ADN , Proteínas de Unión al ADN/genética , Endonucleasas/genética , Femenino , Humanos , Desequilibrio de Ligamiento , Neoplasias Pulmonares/etiología , Masculino , Persona de Mediana Edad , Proteínas Nucleares/genética , Riesgo , Factores de Transcripción/genética , Proteína de la Xerodermia Pigmentosa del Grupo DRESUMEN
Experimental evidence suggests that green tea (Camellia sinesis) may reduce the risk of lung cancer through several hypothesized mechanisms including scavenging oxidative radicals, inhibition of tumor initiation, and modulation of detoxification enzymes. However, epidemiologic results have not been consistent as to the relationship between green tea consumption and lung caner prevention. We employed a population-based case-control study of 122 cases and 122 controls to investigate the effect that green tea consumption may have on the risk of lung cancer and whether polymorphisms in 8-oxoguanine-DNA glycosylase (OGG1), glutathione-S-transferase M1 (GSTM1), and aldo-keto reductase 1C3 (AKR1C3) modify such an association. Daily green tea consumption was associated with a non-significant reduction in lung cancer risk. However, the effect of smoky coal exposure was higher for non-drinkers (odds ratio (OR)=4.93; 95% confidence interval (95% CI)=1.27-19.13) than for drinkers (OR=1.88; 95% CI=1.01-3.48). Further, among individuals with the OGG1 Cys(326) allele, daily consumption was associated with a 72% reduction (95% CI=0.09-0.94). Among GSTM1 null homozygotes, those who consumed green tea daily had a non-significant reduction in risk compared with non-consumers. Green tea consumption had no effect among OGG1 Ser(326) homozygotes or GSTM1 carriers. In addition, AKR1C3 genotype did not modulate the effect of green tea consumption. The chemopreventive effects of green tea in this population may be restricted to individuals who are particularly susceptible to oxidative stress and oxidative DNA damage.
Asunto(s)
Carbón Mineral/análisis , Predisposición Genética a la Enfermedad , Neoplasias Pulmonares/prevención & control , Compuestos Policíclicos/análisis , Té , Oxidorreductasas de Alcohol/genética , Aldehído Reductasa , Aldo-Ceto Reductasas , Estudios de Casos y Controles , ADN Glicosilasas/genética , Femenino , Glutatión Transferasa/genética , Humanos , Neoplasias Pulmonares/etiología , Neoplasias Pulmonares/genética , MasculinoRESUMEN
Lung cancer mortality rates in the Xuan Wei County population are among the highest in China and are associated with exposure to indoor emissions from the burning of smoky coal. Previous studies of lung tumors from both non-smoking women and smoking men in this region showed high frequencies of mutations, consisting mostly of G-->T transversions in the p53 tumor suppressor gene and K-ras oncogene, suggesting that these mutations were caused primarily by polycyclic aromatic hydrocarbons. In this study sputum samples from 92 individuals with no evidence of lung cancer from Xuan Wei County were screened for p53 and K-ras mutations. Sputum cells were collected on glass slides by sputum cytocentrifugation, stained and cytopathologically analyzed. Cytologically non-malignant epithelial cells were taken from each sputum sample using a laser capture microdissection microscope and molecularly analyzed. Cells taken from the sputum of 15 (16.3%) individuals were mutation positive, including 13 (14.1%) individuals each with a p53 mutation, 1 (1.1%) individual with a K-ras mutation and 1 (1.1%) individual with a p53 and a K-ras mutation. p53 mutations were found in both the sputum of individuals with evidence of chronic bronchitis (3 of 46 or 6.5%) and those without evidence of this disease (11 of 46 or 23.9%). Therefore, mutations in the p53 gene and, to a lesser extent, the K-ras gene were frequent in non-malignant epithelial cells taken from the sputum of individuals without evidence of lung cancer who were exposed to smoky coal emissions in Xuan Wei County and were at a high risk for developing the disease.