Particulate Matter Exposure: Genomic Instability, Disease, and Cancer Risk

The United Nations Environment Programme (UNEP/WHO) defines particulate matter (PM) as a mixture of solid or liquid particles suspended and dispersed in the air. Constituted by a complex mixture of organic and inorganic components like metals, acids, soil, and dust is considered a major human carcinogen present in air pollution. When inhaled, PM particles penetrate the respiratory tract, where they affect different organs and systems depending on their aerodynamic size and chemical properties. In the organism, this cocktail-like mixture can interact with cellular mechanisms related to the production of reactive oxygen species (ROS) and can cause damage to important macromolecules such as DNA, lipids, and proteins. Additionally, PM induces a variety of effects at a cellular level, such as inflammation, DNA damage, and genomic instability, acting as a driving force of carcinogenic processes and increasing the incidence of respiratory, cardiopulmonary, neurogenerative, and neurodevelopment disorders. This book chapter reviews the main characteristics of PM, its effects on health, and its role in genomic instability and associated molecular mechanisms. Additionally, we explore different biomarkers associated with PM exposure, DNA damage, and the influence of PM-related oxidative stress in disease development

Modulator effect of hOGG1Ser326Cys polymorphism in micronuclei frequency of populations occupationally exposed to coal mining residues

Introducción: La exposición ocupacional a residuos de minería de carbón puede generar un amplio rango de lesiones en el ADN potencialmente asociadas a procesos carcinogénicos y a otras enfermedades laborales. Objetivo: Evaluar el efecto genotóxico en el ADN de individuos ocupacionalmente expuestos a residuos de minería de carbón mediante la determinación de la frecuencia de micronúcleos (MN) en linfocitos y el posible efecto modulador del polimorfismo de reparo de DNA hOGG1Ser326Cys(rs.1052133). Metodología: Fueron estudiados 74 trabajadores expuestos (GE) y 74 individuos no expuestos de la población general como grupo control (GC), a los cuales se le realizaron las técnicas moleculares test de MN y genotipificación. Resultados: El valor promedio de la frecuencia de MN para el GE fue 8.8±4.9, mientras que el valor promedio para el GC fue de 2.9±4.0. En relación al tiempo de exposición y la frecuencia de MN, individuos con más de 19 años de exposición presentaron una frecuencia de MN mayor (13 – 20 MN) que los individuos entre 2 y 18 años de exposición (2-12 MN). La frecuencia de MN por áreas de trabajo, reveló que los individuos involucrados en actividades de minería presentaron una mayor frecuencia (11.3±3.4), seguidos de los involucrados en embarque (9.0±5.3) y trabajadores del área de acarreo (8.3±5.3). La actividad moduladora del polimorfismo hOGG1Ser326Cys sobre la frecuencia de MN en individuos del GE, evidenció una menor frecuencia (8.32± 4.70) en individuos portadores del polimorfismo Ser/Cys, Cys/Cys con relación a individuos portadores del genotipo Ser/ Ser (9.06± 4.95). Estos hallazgos sobre la posible actividad protectora de hOGG1Ser326Cys en poblaciones expuestas proveen nuevos datos sobre el posible efecto protector de este polimorfismo. Conclusiones: Los datos muestran que la exposición a residuos de minería de carbón genera efectos genotóxicos, y que estos daños son modulados por variantes genotípicas de los genes de reparación involucrados en la remoción de daño oxidativo.Introduction: Occupational exposure to coal mining residues can generate a wide range of DNA lesions potentially associated with carcinogenic processes and other work related diseases. Objetive: To evaluate the genotoxic effects in the DNA of individuals occupationally exposed to coal mining residues considering micronucleus formation in lymphocytes (MN) as endpoints for genotoxicity and the possible modulating effect of DNA repair polymorphism hOGG1Ser326Cys (rs. 1052133). Methodology: The studied population was comprised by 74 exposed workers (GE) and 74 office non-exposed referents from general population as a control group (CG). The mean frequency of MN for GE was 8.8 ± 4.9, while for GC was 2.9 ± 4.0. In regard to time of exposure and MN frequency, individuals over 19 years of exposure presented a higher frequency of MN (13-20 MN) than individuals between 2 and 18 years of exposure (2-12 MN). Results: Frequency of MN discriminated by working areas, revealed that the individuals involved in mining activities had a higher MN frequency (11.3 ± 3.4), followed by those involved in embarking (9.0 ± 5.3) and coal carrying activities (8.3 ± 5.3). Modulatory activity of the hOGG1Ser326Cys polymorphism on MN frequency in GE individuals, showed a lower frequency (8.32 ± 4.70) in individuals carrying the polymorphism Ser / Cys, Cys / Cys compared to Ser / Ser (9.06 ± 4.95) carriers. These findings on the possible protective activity of hOGG1Ser326Cys in exposed populations provide new data to the increasing evidence about the protective role of this polymorphism. Conclusions: Data obtained showed that exposure to coal mining residues generates genotoxic effects that could be modulated by genetic variants of repair genes involved in removal of oxidative damage&nbsp

Modulator effect of hOGG1Ser326Cys polymorphism in micronuclei frequency of populations occupationally exposed to coal mining residues

Introducción: La exposición ocupacional a residuos de minería de carbón puede generar un amplio rango de lesiones en el ADN potencialmente asociadas a procesos carcinogénicos y a otras enfermedades laborales. Objetivo: Evaluar el efecto genotóxico en el ADN de individuos ocupacionalmente expuestos a residuos de minería de carbón mediante la determinación de la frecuencia de micronúcleos (MN) en linfocitos y el posible efecto modulador del polimorfismo de reparo de DNA hOGG1Ser326Cys(rs.1052133). Metodología: Fueron estudiados 74 trabajadores expuestos (GE) y 74 individuos no expuestos de la población general como grupo control (GC), a los cuales se le realizaron las técnicas moleculares test de MN y genotipificación. Resultados: El valor promedio de la frecuencia de MN para el GE fue 8.8±4.9, mientras que el valor promedio para el GC fue de 2.9±4.0. En relación al tiempo de exposición y la frecuencia de MN, individuos con más de 19 años de exposición presentaron una frecuencia de MN mayor (13 – 20 MN) que los individuos entre 2 y 18 años de exposición (2-12 MN). La frecuencia de MN por áreas de trabajo, reveló que los individuos involucrados en actividades de minería presentaron una mayor frecuencia (11.3±3.4), seguidos de los involucrados en embarque (9.0±5.3) y trabajadores del área de acarreo (8.3±5.3). La actividad moduladora del polimorfismo hOGG1Ser326Cys sobre la frecuencia de MN en individuos del GE, evidenció una menor frecuencia (8.32± 4.70) en individuos portadores del polimorfismo Ser/Cys, Cys/Cys con relación a individuos portadores del genotipo Ser/ Ser (9.06± 4.95). Estos hallazgos sobre la posible actividad protectora de hOGG1Ser326Cys en poblaciones expuestas proveen nuevos datos sobre el posible efecto protector de este polimorfismo. Conclusiones: Los datos muestran que la exposición a residuos de minería de carbón genera efectos genotóxicos, y que estos daños son modulados por variantes genotípicas de los genes de reparación involucrados en la remoción de daño oxidativo.Introduction: Occupational exposure to coal mining residues can generate a wide range of DNA lesions potentially associated with carcinogenic processes and other work related diseases. Objetive: To evaluate the genotoxic effects in the DNA of individuals occupationally exposed to coal mining residues considering micronucleus formation in lymphocytes (MN) as endpoints for genotoxicity and the possible modulating effect of DNA repair polymorphism hOGG1Ser326Cys (rs. 1052133). Methodology: The studied population was comprised by 74 exposed workers (GE) and 74 office non-exposed referents from general population as a control group (CG). The mean frequency of MN for GE was 8.8 ± 4.9, while for GC was 2.9 ± 4.0. In regard to time of exposure and MN frequency, individuals over 19 years of exposure presented a higher frequency of MN (13-20 MN) than individuals between 2 and 18 years of exposure (2-12 MN). Results: Frequency of MN discriminated by working areas, revealed that the individuals involved in mining activities had a higher MN frequency (11.3 ± 3.4), followed by those involved in embarking (9.0 ± 5.3) and coal carrying activities (8.3 ± 5.3). Modulatory activity of the hOGG1Ser326Cys polymorphism on MN frequency in GE individuals, showed a lower frequency (8.32 ± 4.70) in individuals carrying the polymorphism Ser / Cys, Cys / Cys compared to Ser / Ser (9.06 ± 4.95) carriers. These findings on the possible protective activity of hOGG1Ser326Cys in exposed populations provide new data to the increasing evidence about the protective role of this polymorphism. Conclusions: Data obtained showed that exposure to coal mining residues generates genotoxic effects that could be modulated by genetic variants of repair genes involved in removal of oxidative damage&nbsp

Neurobehavioral And Oxidative Stress Alterations Following Methylmercury And Retinyl Palmitate Co-Administration In Pregnant And Lactating Rats And Their Offspring

Fish consumption and ubiquitous methylmercury (MeHg) exposure represent a public health problem globally. Micronutrients presented in fish affects MeHg uptake/distribution. Vitamin A (VitA), another fish micronutrient is used in nutritional supplementation, especially during pregnancy. However, there is no information about the health effects arising from their combined exposure. The present study aimed to examine the effects of both MeHg and retinyl palmitate administered to pregnant and lactating rats. Thirty Wistar female rats were orally supplemented with MeHg (0,5 mg/Kg/day) and retinyl palmitate (7500 μg RAE1/Kg/day), either individually or in combination from the gestational day 0 to weaning. In dams, maternal behavior was scored. In neonatal and infant offspring, associative learning and neurodevelopment were evaluated. Further periadolescent male and female pups were assessed for open field, habituation and object recognition using episodic-like memory paradigm. Maternal and offspring redox parameters were evaluated. Our results showed no effects of MeHg-VitA co-administration in the quality of maternal care but showed subtle alterations in the pro-oxidant response of the hippocampus. In offspring, MeHg-VitA co-exposure affected early associative learning in neonatal pups, with no further modifications in neurodevelopment, and no locomotor or exploratory alterations in later developmental stages. Habituation was altered in a sex-dependent manner, but no overall memory disturbances were encountered

Effects Of Methylmercury And Retinol Palmitate Co-Administration In Rats During Pregnancy And Breastfeeding: Metabolic And Redox Parameters In Dams And Their Offspring

Ubiquitous low-dose methylmercury (MeHg) exposure through an increased fish consumption represents a global public health problem, especially among pregnant women. A plethora of micronutrients presented in fish affects MeHg uptake/distribution, but limited data is available. Vitamin A (VitA), another fish micronutrient is used in nutritional supplementation, especially during pregnancy. However, there is no information about the health effects arising from their combined exposure. Therefore, the present study aimed to examine the effects of both MeHg and retinyl palmitate administered on pregnant and lactating rats in metabolic and redox parameters from dams and their offspring. Thirty Wistar female rats were orally supplemented with MeHg (0,5 mg/kg/day) and retinyl palmitate (7500 µg RAE/kg/day) via gavage, either individually or in combination from the gestational day 0 to weaning. For dams (150 days old) and their offspring (31 days old), glycogen accumulation (hepatic and cardiac) and retinoid contents (plasma and liver) were analyzed. Hg deposition in liver tissue was quantified. Redox parameters (liver, kidney, and heart) were evaluated for both animals. Cytogenetic damage was analyzed with micronucleus test. Our results showed no general toxic or metabolic alterations in dams and their offspring by MeHg-VitA co-administration during pregnancy and lactation. However, increased lipoperoxidation in maternal liver and a disrupted pro-oxidant response in the heart of male pups was encountered, with apparently no particular effects in the antioxidant response in female offspring. GST activity in dam kidney was altered leading to possible redox disruption of this tissue with no alterations in offspring. Finally, the genomic damage was exacerbated in both male and female pups. In conclusion, low-dose MeHg exposure and retinyl palmitate supplementation during gestation and lactation produced a potentiated pro-oxidant effect, which was tissue-specific. Although this is a pre-clinical approach, we recommend precaution for pregnant women regarding food consumption, and we encourage more epidemiological studies to assess possible modulations effects of MeHg-VitA co-administration at safe or inadvertently used doses in humans, which may be related to specific pathologies in mothers and their children

Factores ambientales en la transmisión del SARS-CoV-2/COVID 19: panorama mundial y colombiano

Introducción: diversas investigaciones han intentado establecer el impacto de algunos parámetros meteorológicos y de calidad del medio ambiente en la transmisión del SARS-CoV-2, tomando en consideración las características geográficas de cada país y con el fin de mitigar el avance de la enfermedad mediante el control de esos factores. Objetivo: analizar la evidencia existente sobre la posible relación entre factores ambientales y la morbilidad y mortalidad por SARS-CoV-2/COVID-19 en el panorama mundial y colombiano. Metodología: se realizó una revisión exhaustiva de la literatura científica en las bases de datos electrónicas. Además, se analizó el impacto de algunas variables ambientales y la gravedad de los casos de COVID-19 durante el período del 8 de abril al 29 de juliode 2020 en la ciudad Bogotá. Resultados: el análisis correlacional entre la ocupación de camas UCIs en Bogotá con los factores ambientales como temperatura, las concentraciones de PM2.5, O3, NO, NO2 y CO mostraron una relación inversamente significativa. Entre tanto, se presentó una correlación positiva entre los niveles de óxidos de nitrógeno (NO/NO2) y el monóxido de carbono (CO). Algunos de estos resultados posiblemente están relacionados con los efectos de la cuarentena impuesta por el gobierno local. Conclusión: a nivel mundial existe suficiente evidencia para relacionar algunas condiciones y parámetros ambientales con un aumento en la morbilidad y mortalidad por COVID-19. Las evidencias a nivel nacional aún son escasas.Introducción: diversas investigaciones han intentado establecer el impacto de algunos parámetros meteorológicos y de calidad del medio ambiente en la transmisión del SARS-CoV-2, tomando en consideración las características geográficas de cada país y con el fin de mitigar el avance de la enfermedad mediante el control de esos factores. Objetivo: analizar la evidencia existente sobre la posible relación entre factores ambientales y la morbilidad y mortalidad por SARS-CoV-2/COVID-19 en el panorama mundial y colombiano. Metodología: se realizó una revisión exhaustiva de la literatura científica en las bases de datos electrónicas. Además, se analizó el impacto de algunas variables ambientales y la gravedad de los casos de COVID-19 durante el período del 8 de abril al 29 de julio de 2020 en la ciudad Bogotá. Resultados: el análisis correlacional entre la ocupación de camas UCIs en Bogotá con los factores ambientales como temperatura, las concentraciones de PM2.5, O3, NO, NO2 y CO mostraron una relación inversamente significativa. Entre tanto, se presentó una correlación positiva entre los niveles de óxidos de nitrógeno (NO/NO2) y el monóxido de carbono (CO). Algunos de estos resultados posiblemente están relacionados con los efectos de la cuarentena impuesta por el gobierno local. Conclusión: a nivel mundial existe suficiente evidencia para relacionar algunas condiciones y parámetros ambientales con un aumento en la morbilidad y mortalidad por COVID-19. Las evidencias a nivel nacional aún son escasas.Introduction: several investigations have attempted to establish the impact of some meteorological and environmental parameters on the transmission of SARS-CoV-2, considering each country’s geographical characteristics and seeking to mitigate the disease’s advancement by controlling these factors. Objective: Analyze the evidence on the possible relationship between environmental factors, morbidity, and mortality due to SARS-CoV-2/COVID-19, both globally and within Colombia. Methodology: A comprehensive review of the scientific literature was carried out in the electronic databases. Additionally, the impact of some environmental variables and the severity of COVID-19 cases were analyzed during the period from April 8 to July 29, 2020, for the city of Bogotá. Results: The correlational analysis between the ICU admission rates in Bogotá and the environmental factors like temperature, PM2.5, O3, NO, NO2 y CO levels, and ozone concentration showed an inversely significant relationship. Meanwhile, there was a positive correlation between the levels of nitrogen oxides (NO/NO2) and carbon monoxide (CO). Some of these results could be related to the effects of the quarantine imposed by local governments. Conclusion: Globally, there is enough evidence to link environmental conditions and parameters with increased morbidity and mortality for COVID-19. Evidence at the national level is still scarce

Systems chemo-biology analysis of DNA damage response and cell cycle effects induced by coal exposure

Cell cycle alterations are among the principle hallmarks of cancer. Consequently, the study of cell cycle regulators has emerged as an important topic in cancer research, particularly in relation to environmental exposure. Particulate matter and coal dust around coal mines have the potential to induce cell cycle alterations. Therefore, in the present study, we performed chemical analyses to identify the main compounds present in two mineral coal samples from Colombian mines and performed systems chemo-biology analysis to elucidate the interactions between these chemical compounds and proteins associated with the cell cycle. Our results highlight the role of oxidative stress generated by the exposure to the residues of coal extraction, such as major inorganic oxides (MIOs), inorganic elements (IEs) and polycyclic aromatic hydrocarbons (PAH) on DNA damage and alterations in the progression of the cell cycle (blockage and/or delay), as well as structural dysfunction in several proteins. In particular, IEs such as Cr, Ni, and S and PAHs such as benzo[a]pyrene may have influential roles in the regulation of the cell cycle through DNA damage and oxidative stress. In this process, cyclins, cyclin-dependent kinases, zinc finger proteins such as TP53, and protein kinases may play a central role

Micronucleus frequency and exposure to chemical mixtures in three Colombian mining populations

La industria minera colombiana ha experimentado un crecimiento significativo. Dependiendo de la escala y del mineral extraído, se generan mezclas químicas complejas que impactan la salud de las poblaciones ocupacionalmente expuestas y de las comunidades cercanas a los proyectos mineros. Cada vez hay más evidencias que sugieren que la inestabilidad cromosómica (CIN) es un vínculo importante entre el desarrollo de ciertas enfermedades y la exposición a mezclas complejas. Para comprender mejor los efectos de la exposición a mezclas complejas realizamos un estudio de biomonitorización en 407 individuos sanos de cuatro zonas: tres situadas en municipios que explotan sistemas mineros de diferente escala y una zona de referencia sin actividad minera. Se analizaron sistemas de minería a gran, mediana y pequeña escala en Montelíbano (Córdoba), minería artesanal y de pequeña escala (MAPE) en Nechí (Antioquia) y un sistema de minería cerrada en Aranzazu (Caldas). El área de referencia sin actividad minera se estableció en Montería (Córdoba). La ICP-MS midió la exposición multielemental en el cabello, y la NIC se evaluó mediante la técnica de micronúcleos en bloque de citocinesis (MNBN). La exposición a mezclas de elementos químicos fue comparable en trabajadores y residentes de las zonas mineras, pero significativamente superior en comparación con los individuos de referencia. En Montelíbano, el aumento de las frecuencias de MNBN se asoció con la exposición combinada a Se, Hg, Mn, Pb y Mg. Este patrón distintivo difirió significativamente de otras áreas. Específicamente, en Nechí, Cr, Ni, Hg, Se, y Mg emergieron como los principales contribuyentes a las frecuencias elevadas de MNBN. Por el contrario, una combinación de Hg y Ni desempeñó un papel en el aumento de MNBN en Aranzazu. Curiosamente, el Se se correlacionó consistentemente con el aumento de las frecuencias de MNBN en todas las áreas mineras activas. Los elementos químicos en Montelíbano muestran un rango más amplio en comparación con otras zonas mineras, reflejando las características de la minería de alto impacto y a gran escala en la zona. Esta investigación proporciona información valiosa sobre los efectos de la exposición a mezclas químicas, subrayando la importancia de emplear este enfoque en la evaluación del riesgo de las comunidades, especialmente las de las zonas residenciales. © 2023 Los autoresThe Colombian mining industry has witnessed significant growth. Depending on the scale and mineral extracted, complex chemical mixtures are generated, impacting the health of occupationally exposed populations and communities near mining projects. Increasing evidence suggests that chromosomal instability (CIN) is an important link between the development of certain diseases and exposure to complex mixtures. To better understand the effects of exposure to complex mixtures we performed a biomonitoring study on 407 healthy individuals from four areas: three located in municipalities exploiting different-scale mining systems and a reference area with no mining activity. Large, medium, and small-scale mining systems were analyzed in Montelibano (Córdoba), artisanal and small-scale mining (ASGM) in Nechí (Antioquia), and a closed mining system in Aranzazu (Caldas). The reference area with no mining activity was established in Montería (Córdoba). ICP-MS measured multi-elemental exposure in hair, and CIN was evaluated using the cytokinesis-block micronucleus technique (MNBN). Exposure to mixtures of chemical elements was comparable in workers and residents of the mining areas but significantly higher compared to reference individuals. In Montelibano, increased MNBN frequencies were associated with combined exposure to Se, Hg, Mn, Pb, and Mg. This distinct pattern significantly differed from other areas. Specifically, in Nechí, Cr, Ni, Hg, Se, and Mg emerged as the primary contributors to elevated frequencies of MNBN. In contrast, a combination of Hg and Ni played a role in increasing MNBN in Aranzazu. Interestingly, Se consistently correlated with increased MNBN frequencies across all active mining areas. Chemical elements in Montelibano exhibit a broader range compared to other mining zones, reflecting the characteristics of the high-impact and large-scale mining in the area. This research provides valuable insights into the effects of exposure to chemical mixtures, underscoring the importance of employing this approach in the risk assessment of communities, especially those from residential areas. © 2023 The Author

Efeitos biológicos do material particulado gerado em sistemas de mineração de carvão a céu aberto em populações humanas com exposição ambiental

A Colômbia tem uma das maiores reservas de carvão do mundo, sendo o quinto exportador mundial do carvão de tipo térmico. Nos processos de extração de carvão a céu aberto, uma grande quantidade de material particulado (PM), constituído por partículas de pó, hidrocarbonetos e metais pesados, é liberada à atmosfera, onde pode formar misturas complexas e constituir um risco significativo para a saúde, tanto dos indivíduos com exposição ocupacional quanto dos que habitam em proximidade das áreas de mineração. No entanto, em populações humanas, a grande maioria dos dados sobre os efeitos da exposição ao carvão tem sido gerada a partir de estudos em populações com exposição ocupacional, o que faz com que os possíveis efeitos sobre as populações com exposição ambiental sejam desconhecidos. Considerando a pouca informação sobre o tipo de efeitos gerados pela exposição ambiental à resíduos de mineração de carvão, e com a finalidade de melhorar o conhecimento sobre o possível mecanismo do dano em diferentes tecidos, este trabalho teve como objetivo avaliar os efeitos genotóxicos e citotóxicos em populações de indivíduos com exposição ambiental à misturas complexas geradas nos sistemas de mineração de carvão a céu aberto do Departamento de Guajira, Colômbia. Para isso, foram coletados sangue e mucosa oral de 98 indivíduos residentes nas proximidades de uma mina de carvão a céu aberto e de 41 indivíduos não expostos ao carvão. O teste de CBMN-Cyt em linfócitos e BMNCyt em mucosa oral, o ensaio cometa alcalino convencional e modificado com endonucleases (FPG, ENDO III), imunocoração com anticorpos anti-centrômero (CREST), bem como o conteúdo de elementos traço e metais pesados foram avaliados nas amostras. Adicionalmente, as concentrações de PM10 e PM2.5 nas áreas de coleta nas proximidades da mina foram estabelecidas e avaliadas para a presença de metais e matéria orgânica. A análise dos biomarcadores do CBMN-Cyt em linfócitos evidenciou um aumento significativo na frequência de micronúcleos em células binucleadas (MNBN) e células mononucleadas (MNMONO) dos indivíduos com proximidade residencial às áreas de exploração de carvão a céu aberto. As análises sobre a origem dos MN demostraram um aumento significativo de 45.27% na frequência de CREST+ MN nos indivíduos expostos, sugerindo a exposição à substâncias com potencial aneugênico. Particularmente, as frequências de MNBN e a indução de CREST+ MN em residentes expostos demonstraram uma correlação altamente significativa com os níveis de PM2.5, mas não com as concentrações de PM10. A análise geoespacial demonstrou que esta correlação é proporcional à distância entre as populações e as zonas de mineração e que o relevo e a velocidade do vento estão envolvidos na distribuição do PM e o nível de efeito observado em algumas áreas avaliadas. A composição química do PM2.5, avaliada pela técnica de PIXE, evidenciou a presença de elementos traço altamente enriquecidos como o S, e metais pesados moderadamente enriquecidos como Cr, Cu e Zn. O PM2.5 das regiões de mineração também apresentou altas concentrações de matéria orgânica (EOM) com características apolares. Da mesma forma que nos linfócitos, a mucosa oral também mostrou um aumento significativo na frequência de todos os parâmetros do BMNCyt, enquanto que a %Tail DNA, avaliadas no ensaio Cometa convencional e modificado com o uso de endonucleases (FPG e ENDO III), também mostrou um aumento significativo em indivíduos com proximidade residencial às minas de exploração de carvão à céu aberto. Entre os indivíduos expostos, foram detectadas elevadas concentrações sanguíneas de Cr, Ni, Mn e Br quando comparados com os indivíduos não expostos. Os valores de %Tail DNA no ensaio Cometa convencional foram altamente correlacionados com as concentrações de Al, Mn e Br no sangue, enquanto que o %Tail DNA no ensaio Cometa modificado com FPG foi relacionado com as concentrações de Mn. Assim, o dano ao DNA observado nos indivíduos com exposição ambiental à resíduos de mineração de carvão pode ser consequência do dano oxidativo resultante da exposição aos resíduos do carvão, especialmente metais e matéria orgânica contidos na fração fina do material particulado.Colombia has one of the world's largest coal reserves being the fifth biggest thermal coal exporter world-wide. In opencast coal mining extraction, large amounts of particulate matter (PM) constituted by dust particles, hydrocarbons and heavy metals are released into the atmosphere, where they can form complex mixtures, representing a significant health risks to both, occupationally exposed workers and populations living in proximity to mining areas. However, in human populations, most of the data on the effects of exposure to coal residues have been obtained from studies involving occupationally exposed populations, causing a scarcity of data examining the impact of these industrial operations in populations with environmental exposure. Considering the lack of information in regard to the effects of environmental exposure to coal mining residues, and in order to improve our knowledge on the possible damaging mechanism, the aim of this study was to evaluate the genotoxic and cytotoxic effects caused by environmental exposure to complex mixtures generated in open-cast coal mining systems located in the Department of Guajira-Colombia. We collected blood and oral mucosa cells from 98 individuals residents in proximity to an open-pit coal mine and 41 unexposed individuals. We assessed the CBMN-Cyt parameters in lymphocytes and BMNCyt parameters in oral mucosa, the alkaline and endonucleases modified comet assay (FPG, ENDO III), the immunofluorescent antikinetochore staining (CREST) and trace and heavy metals content in samples from exposed individuals. Additionally, PM10 and PM2.5 concentrations were established in sampling areas around the mining zone and metals and organic matter content determined. Analysis of CBMN-Cyt parameters revealed a significant increase in micronuclei frequency in binucleated (MNBN) and mononucleated (MNMONO) cells of individuals with residential proximity to open-pit coal mines compared to residents from non-mining areas. Results on the mechanism of micronucleus formation, showed a statistically significant increase in CREST+ MN (45.27%) in exposed individuals, suggesting the exposure to aneuploidy-inducing substances. Particularly, MNBN frequency and CREST+ MN induction were highly correlated to PM2.5 levels but not to PM10. Spatial interpolation analysis showed that this correlation is proportional to the distance between populations and mining areas. Local wind speed and topography were identified as major contributors to PM dispersion and damage distribution in some areas. Chemical composition of PM2.5 by PIXE demonstrated the presence of highly enriched elements like S and moderate enrichment of heavy metals like Cr, Cu and Zn. Mining regions had also higher concentrations of extractable organic matter (EOM) related to nonpolar and polar compounds. Like in lymphocytes, oral mucosa cells also showed a significant increase of all BMNCyt parameters, while %TailDNA in conventional and endonuclease modified comet assay (FPG and ENDO III) also showed a significant increase in individuals living in proximity to open-pit coal mining areas. Exposed individuals showed higher concentrations of Cr, Ni, Mn and Br in blood compared to unexposed controls. %Tail DNA in conventional Comet assay was highly correlated with Al, Mn and Br concentrations, while %Tail DNA in the FPG Comet assay was correlated to Mn concentrations. These results suggest that DNA damage detected in environmentally exposed individuals may be caused by oxidative damage caused by exposure to coal mining residues, particularly metals and organic matter contented in the fine fraction of the particulate matter

Influência de polimorfismos em genes de metabolismo de xenobióticos e reparação de DNA no risco ocupacional de mineiros de carvão a céu aberto

A Colômbia tem uma das maiores reservas de carvão do mundo, sendo o quinto exportador mundial do carvão de tipo térmico. Nos processos de extração de carvão a céu aberto uma grande quantidade de partículas de pó e metais pesados são liberados à atmosfera, onde podem formar misturas complexas, constituindo um risco significativo para a saúde dos trabalhadores ocupacionalmente expostos. Além disso, nas minas a céu aberto, o carvão extraído é armazenado na presença de luz solar, gerando incêndios espontâneos que constituem uma importante fonte de emissão de Hidrocarbonetos Aromáticos Policíclicos (HAPs) depois de sua combustão incompleta. O objetivo do presente estudo foi avaliar se polimorfismos nos genes do metabolismo de xenobióticos CYP1A1Msp1, GSTM1nulo, GSTT1nulo e de reparação do DNA XRCC1194Trp e OGG1326Cys podem modificar a suscetibilidade individual aos efeitos adversos causados pela exposição aos resíduos de mineração de carvão, considerando a formação de Micronúcleos (MN) e alguns parâmetros do Ensaio Cometa (Índice de Dano - DI, Frequência de dano - DF e porcentagem de DNA na cauda - Tail % DNA) como biomarcadores de mutagenicidade e genotoxicidade. A população de estudo foi formada por 100 trabalhadores de mineração de carvão a céu aberto ocupacionalmente expostos a resíduos de mineração e 100 controles não expostos. O estudo foi realizado na área mineira de “El Cerrejón”, a maior mina de carvão a céu aberto do mundo, localizada em Guajira, ao Norte da Colômbia. As análises dos valores do Ensaio Cometa demonstraram um incremento significativo no DI, DF e porcentagem de DNA na cauda (Tail % DNA) (p < 0,001) no grupo exposto, comparado com o grupo controle. Também houve um aumento significativo na frequência de MN em trabalhadores expostos, representado por um risco relativo (RR) de quase o triplo (2,88, 95% CI 2,525 – 3,284, p < 0,001) para a população exposta, representando um elevado risco de câncer em relação aos controles correspondentes. Apesar destes, os resultados demonstraram que os polimorfismos nos genes do metabolismo (CYP1A1Msp1, GSTM1nulo, GSTT1nulo) e nos genes de reparação do DNA (XRCC1194Trp e OGG1326Cys) não tiveram nenhum impacto sobre as frequências de MN em linfócitos periféricos dos trabalhadores expostos. Da mesma forma, polimorfismos em genes de metabolismo de xenobióticos (GSTM1nulo, GSTT1nulo e CYP1A1Msp1) não influenciaram os níveis de dano no DNA detectados pelo Ensaio cometa. O genótipo XRCC1194Trp/- apresentou uma tendência de proteção em indivíduos expostos, evidenciada em uma diminuição na frequência de MN, embora não tenha sido significante. A nosso conhecimento, este estudo fornece os primeiros dados para a Colômbia sobre o risco genotóxico associado à exposição os resíduos de mineração de carvão a céu aberto e contribui para estabelecer um mapa geral das frequências genotípicas representativas em populações Latino-Americanas, as quais apresentam uma alta complexidade devido ao elevado grau de mistura étnica.Colombia has one of the world's largest coal reserves being the fifth biggest thermal coal exporter world-wide. In open-cast coal mining extraction, large amounts of dust particles and heavy metals are released into the atmosphere, where they can form complex mixtures, representing a significant health risks to occupationally exposed workers. In addition, in open-cast mines, extracted coal is stored under sunlight, causing spontaneous fires, being an important source of Polycyclic Hydrocarbons Aromatic (PHAs) emission after incomplete combustion. The aim of our study was to evaluate if polymorphisms in metabolisms genes CYP1A1Msp1, GSTM1null, GSTT1null and DNA repair XRCC1194Trp and OGG1326Cys could modify individual susceptibility to adverse coal exposure effects caused by the exposition to coal mining residues considering the Micronucleus formation (MN) and Comet Assay parameters (Damage Index (DI), Damage Frequency (DF) and Tail % DNA) as endpoint s for mutagenicity and genotoxicity. The study population comprised 100 open-cast coal mining workers occupationally exposed to coal residues and 100 non-exposed controls. The study was conducted in the coal mining area of “El Cerrejón”, the world’s largest open-cast coal mine, located in Guajira North Colombia. The analysis of Comet assay values indicated a significant increase in the DI, DF and Tail % DNA (p < 0.001) in the exposed group in comparison to the non-exposed control group. There was also a significant MN frequency increase in exposed workers, represented by a relative risk (RR) of almost the triple (2.88, 95% CI 2.525 – 3.284, p < 0.001) for the exposed population, representing a higher risk in relation to the matched non-exposed control. Despite of this, the results show that polymorphisms in the metabolism genes (CYP1A1Msp1,, GSTM1null, GSTT1null) and DNA repair genes (XRCC1194Trp and OGG1326Cys) had no impact on MN frequencies in peripheral lymphocytes of exposed workers. Similarly, polymorphisms in metabolism genes (CYP1A1Msp1,, GSTM1null, GSTT1null) did not influence levels of DNA damage detected by comet assay. XIV The XRCC1194Trp/- genotype shows a protective effect evidenced by a decreased MN frequency in exposed individuals, although with no statistics significance. To our knowledge, this study provides the first data in the country on a genotoxic hazard associated to exposure to coal residues by mining activities and contributes to establishing a general map of representative genotype frequencies in the Latin-American population, which is quite complex given the high degree of ethnic admixture and stratification