RESUMO
The rapid growth of genomics techniques has revolutionized and impacted, greatly and positively, the knowledge of toxicology, ushering it into a "new era": the era of genomic technology (GT). This great advance permits us to analyze the whole genome, to know the gene response to toxicants and environmental stressors, and to determine the specific profiles of gene expression, among many other approaches. The aim of this work was to compile and narrate the recent research on GT during the last 2 years (2020-2022). A literature search was managed using the PubMed and Medscape interfaces on the Medline database. Relevant articles published in peer-reviewed journals were retrieved and their main results and conclusions are mentioned briefly. It is quite important to form a multidisciplinary taskforce on GT with the aim of designing and implementing a comprehensive, collaborative, and a strategic work plan, prioritizing and assessing the most relevant diseases, so as to decrease human morbimortality due to exposure to environmental chemicals and stressors.
Assuntos
Genômica , Toxicologia , Humanos , Genômica/métodos , Substâncias Perigosas , Toxicologia/métodosRESUMO
Lung cancer is the most common neoplasm and the primary cause-related mortality in developed and in most of nondeveloped countries. Epidemiological studies have demonstrated that even at low arsenic doses, the lungs are one of the main target organs and that chronic arsenic exposure has been associated with an increase in lung cancer development. Among the risk factors for cancer, arsenic methylation efficiency (As3MT) and the clearance of arsenic from cells by two members of the ATP-binding cassette (ABC) transporter family (multidrug resistance protein 1 [MRP1] and P-glycoprotein [P-gp]) play an important role in processing of arsenic and decreasing its intracellular levels. This study aimed to evaluate the association between chronic exposure to arsenic with polymorphism of three proteins involved in arsenic metabolism and efflux of the metalloid in subjects with lung cancer. Polymorphism in As3MT, MRP1, and P-gp modified the arsenic metabolism increasing significantly the AsV urinary levels. A significant association between MRP1 polymorphisms with an increase in the risk for cancer was found. The high inorganic arsenic urinary levels registered in the studied subjects suggest a reduction in the efficiency of As3MT, MRP1, and P-gp firstly because of gene polymorphisms and secondarily because of high internal inorganic arsenic levels. MRP1 polymorphism was associated with a twofold increase in the risk of lung cancer.
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Arsênio/metabolismo , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/genética , Metiltransferases/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Polimorfismo Genético/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Arsênio/análise , Arsênio/urina , Estudos de Coortes , Estudos Transversais , Água Potável/análise , Exposição Ambiental , Feminino , Genótipo , Humanos , Neoplasias Pulmonares/epidemiologia , Masculino , Metilação , México/epidemiologia , Pessoa de Meia-Idade , Fatores de Risco , Inquéritos e Questionários , Adulto JovemRESUMO
The objective of this study was to identify and evaluate the impact of exposure to mixtures of organochloride pesticides (OCPs) in agricultural workers by detecting their effects on the activity of the enzyme glutathione S-transferase (GST) and the presence of polymorphisms of the GSTT1 and GSTM1 genes. The presence of OCPs was identified and quantified by gas chromatography, while spectrophotometry was used to measure enzymatic GST activity. The frequencies of the GSTM1 genotypes were analyzed by multiplex PCR. A total of 18 metabolites of OCPs were identified in the workers' blood, most of which are either prohibited (DDT and its metabolites p, p'DDD and p, p'DDE, dieldrin, endrin, aldrin) and/or restricted (δ hexachlorocyclohexane, cis chlordane, methoxychlor, and endosulfan). The results obtained indicate lower levels of GST activity at higher OCPs concentrations detected in blood from exposed workers, together with an increase in OCP levels in individuals who presented the GSTT1*0 and GSTM1*0 genotypes. These conditions place the detoxification process in agricultural workers with null polymorphisms in the GST genes and high concentrations of OCPs in the blood (especially DDT and its metabolites, DDD and DDE) at risk, and increase their susceptibility to develop serious diseases.
Assuntos
Hidrocarbonetos Clorados , Praguicidas , Genótipo , Glutationa Transferase/genética , Humanos , Hidrocarbonetos Clorados/análise , México , Praguicidas/análise , Polimorfismo GenéticoRESUMO
The identification of gene-environment interactions related to breast cancer reveals the biological and molecular mechanisms underlying the disease and allows the distinction of women at high risk from women at lower risk, which could decrease the morbimortality of this neoplasm. The current study evaluated the association between polymorphisms rs1820453 and rs11225161 of the Yes-associated protein (YAP) gene in women with breast cancer exposed to arsenic (As) through drinking water. In total, 182 women were assessed for the frequency of YAP rs1820453 and rs11225161 polymorphisms and As urinary levels. The results demonstrated a positive and significant association between breast cancer and smoking, type of drinking water, and levels of AsIII , AsV and inorganic As (iAs) but not the YAP gene polymorphisms evaluated. In conclusion, our data showed that the source of drinking water and AsV and iAs urinary levels increased the risk for breast cancer, but no interactions between YAP gene polymorphisms and As urinary levels were found.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Arsenicais/efeitos adversos , Neoplasias da Mama/genética , Água Potável/efeitos adversos , Interação Gene-Ambiente , Polimorfismo de Nucleotídeo Único , Fatores de Transcrição/genética , Poluentes Químicos da Água/efeitos adversos , Adulto , Arsenicais/urina , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/etnologia , Estudos Transversais , Feminino , Predisposição Genética para Doença , Humanos , México , Pessoa de Meia-Idade , Fenótipo , Medição de Risco , Fatores de Risco , Fumar/efeitos adversos , Poluentes Químicos da Água/urina , Proteínas de Sinalização YAPRESUMO
BACKGROUND AND PURPOSE: Smoking is a major public health problem worldwide. Polymorphisms in CHRNA3, CHRNA5, and CHRNB4 receptors play a critical role in nicotine dependence, lung cancer (LC) risk, and chronic obstructive pulmonary disease (COPD). This study characterized the CHRNA3 rs1051730 and CHRNA5 rs16969968 polymorphisms in a Mexican population and its association with nicotine dependence, LC, and COPD. METHODS: The study included 312 healthy individuals, 74 LC cases and 117 COPD cases. Genotyping was performed using TaqMan probes, and the data were analyzed using logistic regression adjusted for covariates. RESULTS: The polymorphism CHRNA3 rs1051730 and CHRNA5 rs16969968 were in the Hardy-Weinberg equilibrium and the allelic frequency of the A allele was 0.15, for both polymorphisms. The smokers were stratified in heavy smokers and moderate/light smokers, and we found in A alleles an OR = 2.86 (P = 0.01) to CHRNA3 rs1051730 and OR = 3.12 (P = 0.03) to CHRNA5 rs16969968. In addition, the A alleles in CHRNA3 rs1051730 and CHRNA5 rs16969968 were associated with the risk for LC (OR = 1.66, P = 0.07 and OR = 1.57, P = 0.1, respectively) and for COPD (OR = 2.04, P = 0.01 and OR = 1.91, P = 0.02, respectively). CONCLUSION: CHRNA3/5 polymorphisms are associated with nicotine dependence, LC, and COPD in Mexicans.
Assuntos
Neoplasias Pulmonares/genética , Proteínas do Tecido Nervoso/genética , Doença Pulmonar Obstrutiva Crônica/genética , Receptores Nicotínicos/genética , Fumar/efeitos adversos , Tabagismo/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Estudos Transversais , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Masculino , México , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Adulto JovemRESUMO
PURPOSE: During recent decades, several reports have suggested a decrease in semen quality and DNA damage due in part to environmental toxicants and industrial chemicals. Among these xenobiotics, polycyclic aromatic hydrocarbons (PAHs) are of particular concern because of their remarkable mutagenic and carcinogenic properties and because several experimental and epidemiological studies have reported adverse effects of PAHs on male reproductive health and DNA structure. The aim of the study was to evaluate the association between 1-hydroxypyrene (1-OHP) urinary levels and sperm quality, DNA damage and the frequency of CYP1A1, GSTT1, and GSTM1 polymorphisms. METHODS: Semen, urine and blood samples were taken for sperm-quality assessment, 1-OHP urinary level measurement, DNA damage evaluation and polymorphism frequency analysis of three genes implicated in PAH metabolism in a total of 70 Mexican subjects exposed and nonexposed to PAHs. RESULTS: A significant decrease in sperm quality and increased DNA damage were registered in occupationally exposed volunteers. Polymorphisms modified the 1-OHP urinary levels; however, no associations were found between them. Inverse associations were registered between the sperm concentration/mL and 1-OHP levels and between tail lengths and the GSMT1 null genotype. CONCLUSIONS: Our data showed an inverse association between 1-OHP urinary levels and both sperm quality and the DNA integrity. Additionally, the heterozygote variants of CYP1A1-m1 and CYP1A1-m2 significantly increased the urinary excretion of 1-OHP, and the GSTM1 null variant was inversely associated with the comet parameters evaluated.
Assuntos
Citocromo P-450 CYP1A1/genética , Exposição Ocupacional/efeitos adversos , Hidrocarbonetos Policíclicos Aromáticos/efeitos adversos , Pirenos/urina , Espermatozoides/fisiologia , Adolescente , Adulto , Ensaio Cometa , Citocromo P-450 CYP1A1/urina , Dano ao DNA , Glutationa Transferase/sangue , Glutationa Transferase/genética , Humanos , Entrevistas como Assunto , Modelos Lineares , Masculino , México , Pessoa de Meia-Idade , Hidrocarbonetos Policíclicos Aromáticos/sangue , Hidrocarbonetos Policíclicos Aromáticos/urina , Polimorfismo Genético , Análise do Sêmen , Adulto JovemRESUMO
Exposure to inorganic arsenic (iAs) in drinking water is a global public health concern and is associated with a range of health outcomes, including immune dysfunction. Children are a particularly sensitive population to the effects of inorganic arsenic, yet the biological mechanisms underlying adverse health outcomes are understudied. Here we used a proteomic approach to examine the effects of iAs exposure on circulating serum protein levels in a cross-sectional children's cohort in Mexico. To identify iAs-associated proteins, levels of total urinary arsenic (U-tAs) and its metabolites were determined and serum proteins assessed for differences in expression. The results indicate an enrichment of Tumor Necrosis Factor-(TNF)-regulated immune and inflammatory response proteins that displayed decreased expression levels in relation to increasing U-tAs. Notably, when analyzed in the context of the proportions of urinary arsenic metabolites in children, the most robust response was observed in relation to the monomethylated arsenicals. This study is among the first serum proteomics assessment in children exposed to iAs.
Assuntos
Arsênio/toxicidade , Proteínas Sanguíneas/análise , Exposição Ambiental/efeitos adversos , Arsênio/urina , Arsenicais/urina , Criança , Feminino , Humanos , Masculino , México , Proteômica , Transdução de SinaisRESUMO
Disease manifestations or susceptibilities often differ among individuals exposed to the same concentrations of arsenic (As). These differences have been associated with several factors including As metabolism, sex, age, genetic variants, nutritional status, smoking, and others. This study evaluated the associations between four As metabolism-related gene polymorphisms/null genotypes with urinary As methylation profiles in girls and boys chronically exposed to As. In a total of 332 children aged 6-12 years, the frequency of AS3MT, GSTO1, GSTT1, and GSTM1 polymorphisms/null genotypes and As urinary metabolites were measured. The results revealed that total As and monomethyl metabolites of As (MMA) levels were higher in boys than in girls. No differences in the frequency of the evaluated polymorphisms were found between girls and boys. In AS3MT-Met287Thr carriers, %MMA levels were higher and second methylation levels (defined as dimethylarsinic acid divided by MMA) were lower. In children with the GSTM1 null genotype, second methylation levels were higher. In boys, a positive association between the AS3MT-Met287Thr polymorphism with %MMA and between the GSTO1-Glu155del and As(v) was found; whereas, a negative relationship was identified between AS3MT-Met287Thr and second methylation profiles. In girls, a positive association was found between the GSTO1-Ala140Asp polymorphism with second methylation levels. In conclusion, our data indicate that gender, high As exposure levels, and polymorphisms in the evaluated genes negatively influenced As metabolism. Environ. Mol. Mutagen. 57:516-525, 2016. © 2016 Wiley Periodicals, Inc.
Assuntos
Arsênio/urina , Glutationa Transferase/genética , Metiltransferases/genética , Polimorfismo Genético , Poluentes Químicos da Água/urina , Arsênio/metabolismo , Criança , Exposição Ambiental/análise , Genótipo , Humanos , Metilação , Análise Multivariada , Fatores Sexuais , Fatores de Tempo , População Urbana , Poluentes Químicos da Água/metabolismoRESUMO
The lung is a target organ for adverse health outcomes following exposure to As. Several studies have reported a high prevalence of respiratory symptoms and diseases in subjects highly exposed to As through drinking water; however, most studies to date has been performed in exposed adults, with little information on respiratory effects in children. The objective of the study was to evaluate the association between urinary levels of As and its metabolites with lung function in children exposed in utero and in early childhood to high As levels through drinking water. A total of 358 healthy children were included in our study. Individual exposure was assessed based on urinary concentration of inorganic As. Lung function was assessed by spirometry. Participants were exposed since pregnancy until early childhood to an average water As concentration of 152.13 µg l⻹. The mean urinary As level registered in the studied subjects was 141.2 µg l⻹ and only 16.7% had a urinary concentration below the national concern level. Forced vital capacity was significantly decreased in the studied population and it was negatively associated with the percentage of inorganic As. More than 57% of the subjects had a restrictive spirometric pattern. The urinary As level was higher in those children with restrictive lung patterns when compared with the levels registered in subjects with normal spirometric patterns. Exposure to As through drinking water during in utero and early life was associated with a decrease in forced vital capacity and with a restrictive spirometric pattern in the children evaluated.