Influence of genetic polymorphisms of Hg metabolism and DNA repair on the frequencies of micronuclei, nucleoplasmic bridges, and nuclear buds in communities living in gold mining areas.

Fishing communities living near gold mining areas are at increased risk of mercury (Hg) exposure via bioaccumulation of methylmercury (MeHg) in fish. This exposure has been linked to health effects that may be triggered by genotoxic events. Genetic polymorphisms play a role in the risk associated with Hg exposure. This study evaluated the effect of single nucleotide polymorphisms (SNPs) in metabolic and DNA repair genes on genetic instability and total hair Hg (T-Hg) levels in 78 individuals from "La Mojana" in northern Colombia and 34 individuals from a reference area. Genetic instability was assessed by the frequency of micronuclei (MNBN), nuclear buds (NBUDS), and nucleoplasmic bridges (NPB). We used a Poisson regression to assess the influence of SNPs on T-Hg levels and genetic instability, and a Bayesian regression to examine the interaction between Hg detoxification and DNA repair. Among exposed individuals, carriers of XRCC1Arg399Gln had a significantly higher frequency of MNBN. Conversely, the XRCC1Arg194Trp and OGG1Ser326Cys polymorphisms were associated with lower frequencies of MNBN. XRCC1Arg399Gln, XRCC1Arg280His, and GSTM1Null carriers showed lower NPB frequencies. Our results also indicated that individuals with the GSTM1Nulland GSTT1null polymorphisms had a 1.6-fold risk for higher T-Hg levels. The Bayesian model showed increased MNBN frequencies in carriers of the GSTM1Null polymorphism in combination with XRCC1Arg399Gln and increased NBUDS frequencies in the GSTM1Null carriers with the XRCC3Thr241Met and OGG1Ser326Cys alleles. The GSTM1+ variant was found to be a protective factor in individuals carrying OGG1Ser326Cys (MNBN) and XRCC1Arg280His (NPB); the GSTT1+ polymorphism combined with XRCCArg194Trp also modulated lower MNBN frequencies, while GSTT1+ carriers with the XRCC1Arg399Gln allele showed lower NPB frequencies. Consistent with GSTM1, GSTT1Null carriers with XRCC3Thr241Met showed increased NBUDS frequency. With the rise of gold mining activities, these approaches are vital to identify and safeguard populations vulnerable to Hg's toxic effects.

Evaluación de riesgo de cáncer en personas expuestas ocupacionalmente a solventes orgánicos / Cancer risk evaluation in individuals occupationally exposed to organic solvents

RESUMEN Objetivo Evaluar la frecuencia de micronúcleos (MN) e influencia de los polimorfismos en los genes del metabolismo GSTM1 y GSTT1 como biomarcadores de riesgo de cáncer en pintores de carros (n=152) con respecto a individuos no expuestos (n=152). Métodos Estudio Epidemiológico Molecular, tipo Corte Transversal analítico, interacción gen-ambiente. La evaluación de MNs y polimorfismos genéticos se determinó con pruebas moleculares en linfocitos de los individuos objeto de estudio. Resultados Se determinó que la frecuencia de MNs es 1.6 más alta en el grupo expuesto con relación al grupo referente (1.39±0.92 versus 0,87±0.78, p<0,0001). No se determinó un incremento en la frecuencia de MNs asociado a los polimorfismos en GSTM1 y GSTT1. Conclusiones El incremento de MNs en pintores de carros sirve para alertar al incremento de riesgo de cáncer en esta población expuesta a solventes orgánicos. Estos resultados pueden servir en Programas de Vigilancia Epidemiológica Ocupacional, como estrategia de prevención y en otros países con un amplio sector informal de individuos expuestos a estos químicos para reducir el riesgo de cáncer.(AU)

ABSTRACT Objective To evaluate the frequency of micronuclei (MNs) and influence of GSTM1 and GSTT1 gene polymorphisms as biomarkers of cancer risk in car painters (n=152) compared to unexposed individuals (n=152). Methods Molecular epidemiology study, cross-sectional analysis of gen and environment interaction. The evaluation of MN and genetic polymorphisms was determined by molecular tests in lymphocytes from subjects involved in the study. Results It was determined that the frequency of MNs is 1.6 higher in the exposed group compared to the reference group (1.39 ± 0.92 versus 0.87 ± 0.78, p<0.0001). There was no increase in the frequency of MNs associated with the polymorphisms in GSTM1 and GSTT1. Conclusions The increase of MNs in car painters serves to alert the increased risk of cancer in this population exposed to organic solvents. These results can be used in Occupational Epidemiological Surveillance Programs, as a prevention strategy and policies to regulate and control the use of solvents at a national level and in other countries with a large informal sector of individuals exposed to these chemicals to reduce the risk of cancer.(AU)

[Cancer risk evaluation in individuals occupationally exposed to organic solvents]. / Evaluación de riesgo de cáncer en personas expuestas ocupacionalmente a solventes orgánicos.

OBJECTIVE: To evaluate the frequency of micronuclei (MNs) and influence of GSTM1 and GSTT1 gene polymorphisms as biomarkers of cancer risk in car painters (n=152) compared to unexposed individuals (n=152). METHODS: Molecular epidemiology study, cross-sectional analysis of gen and environment interaction. The evaluation of MN and genetic polymorphisms was determined by molecular tests in lymphocytes from subjects involved in the study. RESULTS: It was determined that the frequency of MNs is 1.6 higher in the exposed group compared to the reference group (1.39 ± 0.92 versus 0.87 ± 0.78, p<0.0001). There was no increase in the frequency of MNs associated with the polymorphisms in GSTM1 and GSTT1. CONCLUSIONS: The increase of MNs in car painters serves to alert the increased risk of cancer in this population exposed to organic solvents. These results can be used in Occupational Epidemiological Surveillance Programs, as a prevention strategy and policies to regulate and control the use of solvents at a national level and in other countries with a large informal sector of individuals exposed to these chemicals to reduce the risk of cancer.

OBJETIVO: Evaluar la frecuencia de micronúcleos (MN) e influencia de los polimorfismos en los genes del metabolismo GSTM1 y GSTT1 como biomarcadores de riesgo de cáncer en pintores de carros (n=152) con respecto a individuos no expuestos (n=152). MÉTODOS: Estudio Epidemiológico Molecular, tipo Corte Transversal analítico, interacción gen-ambiente. La evaluación de MNs y polimorfismos genéticos se determinó con pruebas moleculares en linfocitos de los individuos objeto de estudio. RESULTADOS: Se determinó que la frecuencia de MNs es 1.6 más alta en el grupo expuesto con relación al grupo referente (1.39±0.92 versus 0,87±0.78, p<0,0001). No se determinó un incremento en la frecuencia de MNs asociado a los polimorfismos en GSTM1 y GSTT1. CONCLUSIONES: El incremento de MNs en pintores de carros sirve para alertar al incremento de riesgo de cáncer en esta población expuesta a solventes orgánicos. Estos resultados pueden servir en Programas de Vigilancia Epidemiológica Ocupacional, como estrategia de prevención y en otros países con un amplio sector informal de individuos expuestos a estos químicos para reducir el riesgo de cáncer.

The effect of genetic admixture in an association study: genetic polymorphisms and chromosome aberrations in a Colombian population exposed to organic solvents.

The human population is heterogeneous in genetic susceptibility, chromosomal instability and disease risk; all factors which depend on inherited genetic constitution and acquired nongenetic environmental and occupational factors. Recently, special attention has been directed to the identification of sources of potential bias in population studies of gene-environment interactions including genetic admixture. The aim of this study was to evaluate the effect of genetic admixture in the association of genetic polymorphisms and chromosome aberrations (CA) in a population exposed to organic solvents. We assessed genetic admixture via 34 genetic ancestry informative markers (AIMs) in 398 Colombian individuals. We report a statistically significant difference of higher CA frequency in individuals' below-average European component, and in individuals' above-average Native American component after adjusting for covariates. In addition, the confounding risk ratio values are ≥10% than the adjusted risk ratio, suggesting that population stratification is a confounding factor in this gene-environment association study. Furthermore, after adjusting for individual admixture proportions and covariates, the results demonstrate that glutathione-S-transferase M1 (GSTM1)-null is associated with CA frequency increase. These results suggest that gene-environment association studies that involve recently admixed populations should take into consideration population stratification as a confounding factor and suggest GSTM1-null as a genetic marker associated with CA frequency increase.

Genotoxic and clastogenic effects of monohaloacetic acid drinking water disinfection by-products in primary human lymphocytes.

The haloacetic acids (HAAs) are the second-most prevalent class of drinking water disinfection by-products formed by chemical disinfectants. Previous studies have determined DNA damage and repair of HAA-induced lesions in mammalian and human cell lines; however, little is known of the genomic DNA and chromosome damage induced by these compounds in primary human cells. The aim of this study was to evaluate the genotoxic and clastogenic effects of the monoHAA disinfection by-products in primary human lymphocytes. All monoHAAs were genotoxic in primary human lymphocytes, the rank order of genotoxicity and cytotoxicity was IAA > BAA >> CAA. After 6 h of repair time, only 50% of the DNA damage (maximum decrease in DNA damage) was repaired compared to the control. This demonstrates that primary human lymphocytes are less efficient in repairing the induced damage by monoHAAs than previous studies with mammalian cell lines. In addition, the monoHAAs induced an increase in the chromosome aberration frequency as a measurement of the clastogenic effect of these compounds. These results coupled with genomic technologies in primary human cells and other mammalian non-cancerous cell lines may lead to the identification of biomarkers that may be employed in feedback loops to aid water chemists and engineers in the overall goal of producing safer drinking water.