Micronuclei frequency and exposure to chemical mixtures in three Colombian mining populations.

The 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.

Genetic Instability among Hitnü People Living in Colombian Crude-Oil Exploitation Areas.

Oil exploitation, drilling, transportation, and processing in refineries produces a complex mixture of chemical compounds, including polycyclic aromatic hydrocarbons (PAHs), which may affect the health of populations living in the zone of influence of mining activities (PZOI). Thus, to better understand the effects of oil exploitation activities on cytogenetic endpoint frequency, we conducted a biomonitoring study in the Hitnü indigenous populations from eastern Colombia by using the cytokinesis micronucleus cytome assay (CBMN-cyt). PAH exposure was also measured by determine urine 1-hydroxypyrene (1-OHP) using HPLC. We also evaluated the relationship between DNA damage and 1-OHP levels in the oil exploitation area, as well as the modulating effects of community health factors, such as Chagas infection; nutritional status; and consumption of traditional hallucinogens, tobacco, and wine from traditional palms. The frequencies of the CBMN-cyt assay parameters were comparable between PZOI and Hitnü populations outside the zone of influence of mining activities (POZOI); however, a non-significant incremental trend among individuals from the PZOI for most of the DNA damage parameters was also observed. In agreement with these observations, levels of 1-OHP were also identified as a risk factor for increased MN frequency (PR = 1.20) compared to POZOI (PR = 0.7). Proximity to oil exploitation areas also constituted a risk factor for elevated frequencies of nucleoplasmic bridges (NPBs) and APOP-type cell death. Our results suggest that genetic instability and its potential effects among Hitnü individuals from PZOI and POZOI could be modulated by the combination of multiple factors, including the levels of 1-OHP in urine, malnutrition, and some traditional consumption practices.

Revisão: exposição pré-natal e pesticidas / Revisión: exposición prenatal y pesticidas / Review: Prenatal Exposure and Pesticides

Resumo Introdução: Para uma proteção adequada da saúde humana, especialmente em populações de gestantes e crianças vulneráveis, é necessário estimar com precisão os riscos nos efeitos na saúde da exposição ao pesticida. Objetivo: Identificar por meio de artigos selecionados em pesquisa eletrônica nas bases de dados PubMed y Science Direct que relacionaram os efeitos dos pesticidas com problemas na saúde das mulheres gravidas e seus recém-nascidos. Método: Nesta revisão, foram caracterizados estudos epidemiológicos que avaliam os efeitos na saúde pela exposição aos pesticidas, especialmente organofosforados (OPs) e organoclorados (OCs). Também analisasse estudos nos quais são realizadas avaliações de exposição em gestantes que moram em áreas agrícolas, homens com exposição ocupacional, crianças nascidas e residentes nas áreas onde são utilizados agrotóxicos; estudos associados ao uso de agrotóxicos com anormalidades citogenéticas em recém-nascidos, danos ao DNA e efeitos adversos ao nascer pela exposição aos pesticidas. Resultados: Os resultados dos estudos forneceram evidências para sustentar a hipótese de que a exposição a agrotóxicos está negativamente associada aos efeitos na qualidade de vida de crianças cujos pais estão expostos aos agrotóxicos, uma vez que as crianças estão expostas a diferentes níveis de agrotóxicos durante a gravidez, nascimento e crescimento. Conclusão: A validade dos estudos revisados epidemiológicos y científicos é fortemente reforçada pela avaliação da exposição com base na quantificação dos biomarcadores moleculares.

Resumen Introducción: Para una adecuada protección de la salud humana, especialmente en poblaciones de mujeres embarazadas y niños vulnerables, es necesario estimar con precisión los riesgos en los efectos de la exposición de los plaguicidas en la salud. Objetivo: Identificar artículos seleccionados a través de una búsqueda electrónica en las bases de datos PubMed y Science Direct que relacionaban los efectos de los plaguicidas con problemas de salud en las mujeres embarazadas y sus recién nacidos. Métodos: Esta revisión caracterizó estudios epidemiológicos que evalúan los efectos sobre la salud de la exposición a los plaguicidas, especialmente los organofosforados (OP) y los organoclorados (OC). También se analizaron estudios en los que se evaluó la exposición en mujeres embarazadas que viven en zonas agrícolas, hombres con exposición ocupacional, niños nacidos y residentes en zonas donde se utilizan plaguicidas, estudios asociados al uso de plaguicidas con anomalías citogenéticas en los recién nacidos, daños en el ADN y efectos adversos al nacimiento por exposición a plaguicidas. Resultados: Los resultados de los estudios aportaron pruebas que apoyan la hipótesis de que la exposición a los plaguicidas se asocia negativamente con los efectos en la calidad de vida de los niños cuyos padres están expuestos a los plaguicidas, ya que los niños están expuestos a diferentes niveles de plaguicidas durante el embarazo, el embarazo, el nacimiento y el crecimiento. Conclusión: La validez de los estudios epidemiológicos y científicos revisados se ve muy reforzada por la evaluación de la exposición basada en la cuantificación de biomarcadores moleculares.

Factores ambientales en la transmisión del SARS-CoV-2/COVID 19: panorama mundial y colombiano / Environmental factors in the transmission of SARS-COV-2/COVID 19: World and Colombian outlook

Resumen 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: 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.

Abstract 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.

Dietary exposure to mercury and its relation to cytogenetic instability in populations from "La Mojana" region, northern Colombia.

Fish consumption and chronic exposure to low doses of mercury (Hg) seems to activate several molecular mechanisms leading to carcinogenic and/or teratogenic processes. However, Hg genotoxic effects on humans are not completely described. In the present study, we assessed cytogenetic damage in isolated human peripheral lymphocytes using the cytokinesis-block micronucleus cytome assay (CBMN-Cyt), micronucleus formation with anti-kinetochore antibody (CREST staining), levels of total Hg in hair (T-Hg), fish consumption, and estimated Hg dose. The study comprised 39 non-exposed, and 73 residents from La Mojana region, an area with a well-documented Hg contamination. Data showed a significant increase in micronuclei (MNBN), nucleoplasmic bridges (NPB), and necrotic and apoptotic cell frequencies in residents of "La Mojana." The overall mean T-Hg level in hair for exposed residents was 1.12 ± 0.94 mg kg-1 and 0.15 ± 0.05 in individuals from the reference area. Approximately 40% of analyzed individuals showed T-Hg levels that exceeded US Environmental Protection Agency (USEPA) reference dose. Increased T-Hg levels in hair were related to increased MNBN frequencies and high fish consumption. Other cellular markers, such as necrotic and apoptotic cell frequencies, were also correlated with high fish intake and T-Hg contents. Results of the CREST staining demonstrated that in vivo exposure to Hg induces genetic instability by chromosome fragment loss (clastogenic). Additionally, a high average intake of some fish species, particularly with carnivorous habits like Caquetaia kraussii, Hoplias malabaricus, and Sorubin cuspicaudus, seems to increase MNBN frequencies significantly.

Nuclear factor erythroid 2 - related factor 2 and its relationship with cellular response in nickel exposure: a systems biology analysis.

BACKGROUND: Nickel and nickel-containing compounds (NCC) are known human carcinogens. However, the precise molecular mechanisms of nickel-induced malignant transformation remain unknown. Proposed mechanisms suggest that nickel and NCC may participate in the dual activation/inactivation of enzymatic pathways involved in cell defenses against oxidative damage, where Nuclear factor-erythroid 2 related factor 2 (Nrf2) plays a central role. METHODS: For assessing the potential role of proteins involved in the Nrf2-mediated response to nickel and NCC exposure, we designed an interactome network using the STITCH search engine version 5.0 and the STRING software 10.0. The major NCC-protein interactome (NCPI) generated was analyzed using the MCODE plugin, version 1.5.1 for the detection of interaction modules or subnetworks. Main centralities of the NCPI were determined with the CentiScape 2.2 plugin of Cytoscape 3.4.0 and main biological processes associated with each cluster were assessed using the BiNGO plugin of Cytoscape 3.4.0. RESULTS: Water-soluble NiSO4 and insoluble Ni3S2 were the most connected to proteins involved in the NCPI network. Nfr2 was detected as one of the most relevant proteins in the network, participating in several multifunctional protein complexes in clusters 1, 2, 3 and 5. Ontological analysis of cluster 3 revealed several processes related to unfolded protein response (UPR) and response to endoplasmic reticulum (ER) stress. CONCLUSIONS: Cellular response to NCC exposure was very comparable, particularly concerning oxidative stress response, inflammation, cell cycle/proliferation, and apoptosis. In this cellular response, Nfr2 was highly centralized and participated in several multifunctional protein complexes, including several related to ER-stress. These results add evidence on the possible Ni2+ induced - ER stress mainly associated with insoluble NCC. In this scenario, we also show how protein degradation mediated by ubiquitination seems to play key roles in cellular responses to Ni.

Genetic damage in environmentally exposed populations to open-pit coal mining residues: Analysis of buccal micronucleus cytome (BMN-cyt) assay and alkaline, Endo III and FPG high-throughput comet assay.

DNA and chromosomal damage in individuals occupationally exposed to coal mining residues have repeatedly been reported in lymphocytes and epithelial cells, suggesting a systemic exposure-response in which generation of oxidative damage may play a major role. Nevertheless, the understanding of this mechanism is still incomplete, particularly in regard to environmental exposures. This study aimed to evaluate DNA damage using the cytome assay (BMN-cyt) in buccal cells and its relation to primary and oxidative DNA damage in lymphocytes, assessed by the high-throughput alkaline and modified (FPG-ENDO III) Comet assay in individuals with environmental exposure to coal mining residues in northern Colombia. Considering metals from coal mining activities as the main source of reactive oxygen species (ROS) generation, the concentrations of inorganic elements in blood samples was also assessed. The analysis revealed that frequencies of BMN-cyt parameters related to DNA damage (micronuclei), cytokinesis (binucleated cells) and cell death (condensed chromatin, karyorrhexis, pyknosis and karyolysis) were significantly higher in individuals that were environmentally exposed to coal compared to the unexposed group. The level of % Tail DNA in the alkaline and the modified Comet assay was 4.0 and 4.3 times higher among exposed individuals than in unexposed controls respectively. Increased MN frequencies in buccal cells were correlated with increased %Tail DNA in alkaline and FPG Comet assay. Additionally, exposed individuals had higher concentrations of Cr, Ni, Mn, and Br in the blood compared to unexposed controls. %Tail DNA in alkaline Comet assay was highly correlated with Al, Mn, and Br concentrations, while %Tail DNA in the FPG Comet assay correlated with Mn levels. These results suggest that oxidative damage, particularly purine oxidation, may play an essential role in DNA damage in individuals exposed to coal residues and that some inorganic elements are related to this effect.

Geospatial analysis of residential proximity to open-pit coal mining areas in relation to micronuclei frequency, particulate matter concentration, and elemental enrichment factors.

During coal surface mining, several activities such as drilling, blasting, loading, and transport produce large quantities of particulate matter (PM) that is directly emitted into the atmosphere. Occupational exposure to this PM has been associated with an increase of DNA damage, but there is a scarcity of data examining the impact of these industrial operations in cytogenetic endpoints frequency and cancer risk of potentially exposed surrounding populations. In this study, we used a Geographic Information Systems (GIS) approach and Inverse Distance Weighting (IDW) methods to perform a spatial and statistical analysis to explore whether exposure to PM2.5 and PM10 pollution, and additional factors, including the enrichment of the PM with inorganic elements, contribute to cytogenetic damage in residents living in proximity to an open-pit coal mining area. Results showed a spatial relationship between exposure to elevated concentrations of PM2.5, PM10 and micronuclei frequency in binucleated (MNBN) and mononucleated (MNMONO) cells. Active pits, disposal, and storage areas could be identified as the possible emission sources of combustion elements. Mining activities were also correlated with increased concentrations of highly enriched elements like S, Cu and Cr in the atmosphere, corroborating its role in the inorganic elements pollution around coal mines. Elements enriched in the PM2.5 fraction contributed to increasing of MNBN but seems to be more related to increased MNMONO frequencies and DNA damage accumulated in vivo. The combined use of GIS and IDW methods could represent an important tool for monitoring potential cancer risk associated to dynamically distributed variables like the PM.

Cytogenetic instability in populations with residential proximity to open-pit coal mine in Northern Colombia in relation to PM10 and PM2.5 levels.

Epidemiological studies indicate that living in proximity to coal mines is correlated with numerous diseases including cancer, and that exposure to PM10 and PM2.5 components could be associated with this phenomenon. However, the understanding of the mechanisms by which PM exerts its adverse effects is still incomplete and comes mainly from studies in occupationally exposed populations. The aims of this study were to: (1) evaluate DNA damage in lymphocytes assessing the cytokinesis-block micronucleus cytome assay (CBMN-cyt) parameters; (2) identify aneugenic or clastogenic effects in lymphocytes of exposed populations using CREST immunostaining for micronuclei; (3) evaluate multi-elemental composition of atmospheric particulate matter; and (4) verify relation between the DNA damage and PM2.5 and PM10 levels around the mining area. Analysis 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. Correlation analysis demonstrated a highly significant association between PM2.5 levels, MNBN frequencies and CREST+ micronuclei induction in exposed residents. These results suggest that PM2.5 fraction generated in coal mining activities may induce whole chromosome loss (aneuploidy) preferentially, although there are also chromosome breaks. Analysis of the chemical composition of PM2.5 by PIXE demonstrated that Si, S, K and Cr concentrations varied significantly between coal mining and reference areas. Enrichment factor values (EF) showed that S, Cr and Cu were highly enriched in the coal mining areas. Compared to reference area, mining regions had also higher concentrations of extractable organic matter (EOM) related to nonpolar and polar compounds. Our results demonstrate that PM2.5 fraction represents the most important health risk for residents living near open-pit mines, underscoring the need for incorporation of ambient air standards based on PM2.5 measures in coal mining areas.

Polymorphisms in metabolism and repair genes affects DNA damage caused by open-cast coal mining exposure.

Increasing evidence suggest that occupational exposure to open-cast coal mining residues like dust particles, heavy metals and Polycyclic Aromatic Hydrocarbons (PAHs) may cause a wide range of DNA damage and genomic instability that could be associated to initial steps in cancer development and other work-related diseases. The aim of our study was to evaluate if key polymorphisms in metabolism genes CYP1A1Msp1, GSTM1Null, GSTT1Null and DNA repair genes XRCC1Arg194Trp and hOGG1Ser326Cys could modify individual susceptibility to adverse coal exposure effects, considering the DNA damage (Comet assay) and micronucleus formation in lymphocytes (CBMN) and buccal mucosa cells (BMNCyt) as endpoints for genotoxicity. The study population is comprised of 200 healthy male subjects, 100 open-cast coal-mining workers from "El Cerrejón" (world's largest open-cast coal mine located in Guajira - Colombia) and 100 non-exposed referents from general population. The data revealed a significant increase of CBMN frequency in peripheral lymphocytes of occupationally exposed workers carrying the wild-type variant of GSTT1 (+) gene. Exposed subjects carrying GSTT1null polymorphism showed a lower micronucleus frequency compared with their positive counterparts (FR: 0.83; P=0.04), while BMNCyt, frequency and Comet assay parameters in lymphocytes: Damage Index (DI) and percentage of DNA in the tail (Tail % DNA) were significantly higher in exposed workers with the GSTM1Null polymorphism. Other exfoliated buccal mucosa abnormalities related to cell death (Karyorrhexis and Karyolysis) were increased in GSTT/M1Null carriers. Nuclear buds were significantly higher in workers carrying the CYP1A1Msp1 (m1/m2, m2/m2) allele. Moreover, BMNCyt frequency and Comet assay parameters were significantly lower in exposed carriers of XRCC1Arg194Trp (Arg/Trp, Trp/Trp) and hOGG1Ser326Cys (Ser/Cys, Cys/Cys), thereby providing new data to the increasing evidence about the protective role of these polymorphisms. This modulation may involve specific and differentiated pathways in different tissues that also may cause a differential sensitivity related to differential induction of some enzymes.