ABSTRACT Introduction: Lung cancer is one of the main health problems in Cuba and worldwide. Genetic differences due to single nucleotide polymorphisms are important factors involved in the genetic susceptibility to this disease. In Cuba, there are scarce data available on single nucleotide polymorphisms and their possible influence on the incidence and prognosis of cancer. Objective: To expose the importance of the study of single nucleotide polymorphisms in DNA damage repair genes in lung cancer. Results: Smoking is the main risk factor for developing lung cancer, however, approximately 15 % of smokers will develop the disease. Single nucleotide polymorphisms are important factors involved in genetic predisposition to diseases. The presence of polymorphic variants can modify the efficacy of repair systems, favoring the occurrence of genotoxicity and/or mutagenesis. They can also modify the response to oncological treatments and patient´s survival. Therefore, in addition to being susceptibility markers, polymorphisms are considered individual prognostic markers of response to therapy. This work emphasizes the usefulness of evaluating single nucleotide polymorphisms as clinical and susceptibility biomarkers in the Cuban population. Conclusions. The study of single nucleotide polymorphisms will allow a personalized approach to oncological diseases, which could contribute to define groups of individuals at high risk of getting lung cancer, therefore, early disease detection.

RESUMEN Introducción: El cáncer de pulmón es uno de los principales problemas de salud en Cuba y el mundo. Las diferencias genéticas a causa de polimorfismos de un solo nucleótido, son factores importantes involucrados en la susceptibilidad genética a esta enfermedad. En Cuba son escasos los datos disponibles sobre los polimorfismos de un solo nucleótido y su posible influencia sobre la aparición y pronóstico del cáncer. Objetivo: Exponer la importancia del estudio de los polimorfismos de un solo nucleótido en genes de la reparación del daño al ADN en el cáncer de pulmón. Desarrollo: El tabaquismo es el principal factor de riesgo para desarrollar cáncer de pulmón, sin embargo, aproximadamente el 15 % de los fumadores desarrollará la enfermedad. Los polimorfismos de un solo nucleótido son factores involucrados en la predisposición genética a las enfermedades. La presencia de variantes polimórficas puede modificar la eficacia de los sistemas de reparación, favoreciendo la aparición de genotoxicidad y/o mutagénesis. También pueden modificar la respuesta a los tratamientos oncológicos y la supervivencia de los pacientes. Por consiguiente, además de ser marcadores de susceptibilidad, los polimorfismos se consideran marcadores de pronóstico individual de respuesta a la terapia. Este trabajo enfatiza la utilidad de su evaluación como biomarcadores clínicos y de susceptibilidad genética a enfermedades en la población cubana. Conclusiones: El estudio de polimorfismos de un solo nucleótido permitirá el abordaje personalizado de enfermedades oncológicas, lo cual podría contribuir a su detección temprana y a definir grupos de individuos con alto riesgo de padecer cáncer de pulmón.

ABSTRACT INTRODUCTION The consequences of de novo balanced structural chromosome aberrations diagnosed antenatally are unpredictable, and, as a result, they introduce uncertainty into genetic counseling decisions. OBJECTIVE Describe de novo balanced structural aberrations present at antenatal diagnosis in samples from pregnant women in five Latin American countries and determine their effect on carrier individuals. METHODS This was a retrospective observational study based on analysis of 109,011 antenatal tests conducted from January 1981 to December 2016 in Cuba, Uruguay, Costa Rica, Mexico, and Colombia. Thirteen cytogenetic laboratories provided information that included the cases analyzed during the study period; number of de novo balanced structural aberrations diagnosed antenatally; number of diagnoses with de novo balanced structural aberrations that resulted in termination of pregnancy; detailed descriptions of the karyotypes of de novo balanced structural aberration carriers, and descriptions of the form of diagnosis, including types of samples used (amniotic fluid, chorionic villus or fetal blood). Each laboratory also provided pathology reports and genetic counseling at time of diagnosis. Postnatal followup for pregnancies carried to term continued for at least two years. RESULTS Of the 109,011 antenatal tests studied, 72 (0.07%) showed de novo balanced structural aberrations. These events primarily involved chromosomes 1, 2, 7, 14, 18, and 20. Of the 79 breakpoints identified, the most common were 5p15.3, 7q11.2, 7q22, and 14q24. We identified three breakpoints corresponding to 3.8% (3q13.1, 3q13.2, and 9p12) that were not reported in other studies of de novo balanced structural aberrations diagnosed antenatally in patients from other geographic regions or in studies of chromosomal fragile sites. Two of these breakpoints (3q13.1 and 3q13.2) were associated with high risk of phenotypic abnormalities. Information on antenatal or postnatal followup was available for 62 (86%) of de novo balanced structural aberration carriers; of the 44 carriers with postnatal followup, 10 had phenotypic abnormalities. CONCLUSIONS Three new de novo breakpoints were identified, presumably related to genetic admixture characteristics in Latin America. Since some diseases associated with de novo balanced structural aberrations detected antenatally have a late onset, followup for at least two years is recommended for carriers of these aberrations. The information in this study is useful in genetic counseling for pregnant women in Latin America.

INTRODUCTION: Vimang® is a product of natural origin obtained from the mango tree (Manguifera indica L. Anacardiaceae family. This compound has been classified as antioxidant, immunomodulation agent, etc. Thus, it is important to know its cytotoxic potential. OBJECTIVES: to assess the cytotoxicity of a aqueous extract of Vimang®. METHODS: the prokaryotic (PQ37 strain-Escherichia coli and eukaryotic (human erutjrocytes) models and cellular survival curves with PQ37 strain (with and without metabolic activation) were made and the levels of alkaline phosphatase were quantified (by Chromotest SOS test). Later, a trial of mitochondria activity was developed in erythrocytes. The concentrations of study Vimang® were: 50, 250, 500 and 1 000 µg of lyophilized/mL extract. RESULTS: the prokaryotic trial indicated that, in absence of S9, Vimang® decrease significantly the cell viability when it is applied at a concentration similar o higher than 500 µg/mL. However, the presence of a metabolic activation could to cause a biotransformation of the Vimang's® components leading to the no-cytotoxicity of product within the study concentration rank. Analysis of alkaline phosphatase levels quantified in presence of Vimang® suggested that the cytotoxicity detected in PQ37 Escherichia coli apparently isn't related to protein synthesis inhibition. In the case of the eukaryotic trial used and the assayed concentrations, the cell survival of erythrocytes (in presence of Vimang® not decreased significantly in relation to the corresponding controls. CONCLUSIONS: Vimang® is cytotoxic for the PQ37 strain of E.coli when it is applied at a concentration similar or higher than 500 µg/mL. This effect is not observed in these cells neither when a metabolic activation is applied nor in the human erythrocytes for the conditions reported in present paper.

INTRODUCCIÓN: Vimang® es un producto de origen natural que se obtiene del árbol del mango (Manguifera indica L. familia Anacardiaceae). Este compuesto ha sido clasificado como antioxidante, inmunomodulador, etc. Por ello, resulta importante conocer su potencial citotóxico. OBJETIVOS: evaluar la citotoxicidad de un extracto acuoso del Vimang®. MÉTODOS: se emplearon los modelos procariótico (Escherichia coli, cepa PQ37) y eucariótico (eritrocitos humanos), se realizaron curvas de supervivencia celular con la cepa PQ37 (con activación metabólica y sin esta); así como se cuantificaron los niveles de la actividad fosfatasa alcalina (mediante la realización del SOS Chromotest). Posteriormente, se desarrolló el ensayo de inhibición de la actividad mitocondrial en eritrocitos. Las concentraciones de Vimang® estudiadas fueron: 50, 250, 500 y 1 000 mg de extracto liofilizado/mL. RESULTADOS: el ensayo procariótico indicó que, en ausencia de fracción S9, el Vimang® diminuye significativamente la viabilidad celular cuando se aplica a concentración igual o superior que 500 mg/mL. Sin embargo, la presencia de activación metabólica podría ocasionar una biotransformación de los componentes del Vimang® que conduce a la no citotoxicidad del producto en el rango de concentraciones analizado. El análisis de los niveles de fosfatasa alcalina cuantificados en presencia del Vimang®; sugirió que la citotoxicidad detectada en E. coli PQ37 no parece estar relacionada con la inhibición de la síntesis proteica. En el caso del ensayo eucariótico empleado y las concentraciones ensayadas, la supervivencia celular de los eritrocitos (en presencia de Vimang®)no disminuyó de forma significativa en relación con los controles correspondientes. CONCLUSIONES: el Vimang® es citotóxico para la cepa PQ37 de Escherichia coli cuando se aplica a una concentración igual o superior que 500 mg/mL. Este efecto no se observa en estas células cuando se emplea activación metabólica ni en eritrocitos humanos para las condiciones reportadas en este trabajo.