Combining biomarkers of susceptibility with toxicodynamic models: a novel approach for assessing modifying factors.

Biomarkers of susceptibility are indicative of an individual's capacity to react to particular exposures, whereas toxicodynamic models elucidate the correlation between exposure and response. In this article, a novel methodology is presented for the evaluation of modifying factors in the field of toxicology. The proposed approach involves the integration of biomarkers of susceptibility with toxicodynamic models. Through the integration of these two methodologies, scientists are able to gain a more comprehensive understanding of the impact of modifying factors, such as genetic polymorphisms or epigenetic profiles, on an individual's reaction to toxic substances. This methodology has the potential to facilitate a more thorough evaluation of the hazards linked to the contact with combinations of chemicals and the cumulative effects of such exposures. The utilization of biomarkers in the evaluation of exposure for risk assessment is progressively incorporating the examination of susceptibility factors alongside exposure factors. This may involve the identification of a particular genetic polymorphism for a metabolic enzyme. The integration of ecotoxicological tests with models is crucial for achieving a comprehensive assessment. This approach exhibits the potential to enhance our comprehension of disease causation and facilitate the identification of populations that may exhibit an elevated susceptibility to disease.

Genetic Aspects of Susceptibility to Mercury Toxicity: An Overview.

Human exposure to mercury is still a major public health concern. In this context, children have a higher susceptibility to adverse neurological mercury effects, compared to adults with similar exposures. Moreover, there exists a marked variability of personal response to detrimental mercury action, in particular among population groups with significant mercury exposure. New scientific evidence on genetic backgrounds has raised the issue of whether candidate susceptibility genes can make certain individuals more or less vulnerable to mercury toxicity. In this review, the aim is to evaluate a new genetic dimension and its involvement in mercury risk assessment, focusing on the important role played by relevant polymorphisms, located in attractive gene targets for mercury toxicity. Existing original articles on epidemiologic research which report a direct link between the genetic basis of personal vulnerability and different mercury repercussions on human health will be reviewed. Based on this evidence, a careful evaluation of the significant markers of susceptibility will be suggested, in order to obtain a powerful positive "feedback" to improve the quality of life. Large consortia of studies with clear phenotypic assessments will help clarify the "window of susceptibility" in the human health risks due to mercury exposure.

Identification of drug-induced toxicity biomarkers for treatment determination.

Drug-induced organ toxicity (DIOT) that leads to the removal of marketed drugs or termination of candidate drugs has been a leading concern for regulatory agencies and pharmaceutical companies. In safety studies, the genomic assays are conducted after the treatment so that drug-induced adverse effects can occur. Two types of biomarkers are observed: biomarkers of susceptibility and biomarkers of response. This paper presents a statistical model to distinguish two types of biomarkers and procedures to identify susceptible subpopulations. The biomarkers identified are used to develop classification model to identify susceptible subpopulation. Two methods to identify susceptibility biomarkers were evaluated in terms of predictive performance in subpopulation identification, including sensitivity, specificity, and accuracy. Method 1 considered the traditional linear model with a variable-by-treatment interaction term, and Method 2 considered fitting a single predictor variable model using only treatment data. Monte Carlo simulation studies were conducted to evaluate the performance of the two methods and impact of the subpopulation prevalence, probability of DIOT, and sample size on the predictive performance. Method 2 appeared to outperform Method 1, which was due to the lack of power for testing the interaction effect. Important statistical issues and challenges regarding identification of preclinical DIOT biomarkers were discussed. In summary, identification of predictive biomarkers for treatment determination highly depends on the subpopulation prevalence. When the proportion of susceptible subpopulation is 1% or less, a very large sample size is needed to ensure observing sufficient number of DIOT responses for biomarker and/or subpopulation identifications.

Exposición ambiental a plaguicidas: biomarcadores en matrices de la tríada madre-placenta-feto / Environmental exposure to pesticides: biomarkers in matrices of the mother-placenta-fetus triad / Exposição ambiental aos agrotóxicos: biomarcadores em matrizes do tríade mãe-placenta-feto

El biomonitoreo tiene un papel fundamental en la evaluación de la salud ambiental de poblaciones expuestas a contaminantes. Este artículo analiza información referente a biomarcadores de exposición y susceptibilidad así como también a biomarcadores de efecto que pueden ser útiles en estrategias diagnósticas y preventivas en la exposición a plaguicidas persistentes (órganoclorados) y a plaguicidas moderadamente persistentes (órganofosforados), en un período de alta vulnerabilidad como el embarazo. También revisa diferentes estudios en los que se ha observado correlación entre biomarcadores de exposición en matrices de la tríada madre-placentafeto y el impacto en el desarrollo del embarazo y el crecimiento intrauterino así como también en la funcionalidad del cerebro en la infancia. Finalmente, este trabajo describe noveles biomarcadores inespecíficos entre los que se incluyen biomarcadores epigenéticos, de estrés oxidativo, de disrupción endocrina y de expresión genética.

Biomonitoring plays a key role in the assessment of environmental health of populations exposed to pollutants. This paper analyzes information regarding biomarkers of exposure and biomarkers of susceptibility as well as biomarkers of effect that may be useful in diagnostic and preventive strategies in the exposure to persistent pesticides (organochlorine) and moderately persistent pesticides (organophosphates) in a period of high vulnerability as pregnancy. It also reviews different studies where correlation between biomarkers of exposure in matrices of the mother-placenta-feto triad and the impact on the course of pregnancy and fetal growth as well as the functionality of the brain in childhood has been observed. Finally, this work describes nonspecific novel biomarkers including epigenetic biomarkers, biomarkers of oxidative stress, endocrine disruption and gene expression.

O biomonitoramento desempenha um papel fundamental na avaliação da saúde ambiental de populações expostas a contaminantes. Este artigo analisa informações sobre biomarcadores de exposição e de susceptibilidade, bem como biomarcadores de efeito, que podem ser úteis em estratégias de diagnóstico e de prevenção na exposição a pesticidas persistentes (organoclorados) e a pesticidas moderadamente persistentes (organofosforados), em um período de alta vulnerabilidade, tal como a gravidez. Ele também revisa vários estudos nos quais tem sido observada correlação entre biomarcadores de exposição em matrizes da tríade mãe-placenta-feto e o impacto no desenvolvimento da gestação e no crescimento intra-uterino, bem como na funcionalidade do cérebro na infância. Finalmente, este artigo descreve biomarcadores inespecíficos nóveis incluindo biomarcadores epigenéticos, de estresse oxidativo, de disrupção endócrina e de expressão gênica.

Exposición ambiental a plaguicidas: biomarcadores en matrices de la tríada madre-placenta-feto / Environmental exposure to pesticides: biomarkers in matrices of the mother-placenta-fetus triad / ExposiþÒo ambiental aos agrotóxicos: biomarcadores em matrizes do tríade mÒe-placenta-feto

El biomonitoreo tiene un papel fundamental en la evaluación de la salud ambiental de poblaciones expuestas a contaminantes. Este artículo analiza información referente a biomarcadores de exposición y susceptibilidad así como también a biomarcadores de efecto que pueden ser útiles en estrategias diagnósticas y preventivas en la exposición a plaguicidas persistentes (órganoclorados) y a plaguicidas moderadamente persistentes (órganofosforados), en un período de alta vulnerabilidad como el embarazo. También revisa diferentes estudios en los que se ha observado correlación entre biomarcadores de exposición en matrices de la tríada madre-placentafeto y el impacto en el desarrollo del embarazo y el crecimiento intrauterino así como también en la funcionalidad del cerebro en la infancia. Finalmente, este trabajo describe noveles biomarcadores inespecíficos entre los que se incluyen biomarcadores epigenéticos, de estrés oxidativo, de disrupción endocrina y de expresión genética.(AU)

Biomonitoring plays a key role in the assessment of environmental health of populations exposed to pollutants. This paper analyzes information regarding biomarkers of exposure and biomarkers of susceptibility as well as biomarkers of effect that may be useful in diagnostic and preventive strategies in the exposure to persistent pesticides (organochlorine) and moderately persistent pesticides (organophosphates) in a period of high vulnerability as pregnancy. It also reviews different studies where correlation between biomarkers of exposure in matrices of the mother-placenta-feto triad and the impact on the course of pregnancy and fetal growth as well as the functionality of the brain in childhood has been observed. Finally, this work describes nonspecific novel biomarkers including epigenetic biomarkers, biomarkers of oxidative stress, endocrine disruption and gene expression.(AU)

O biomonitoramento desempenha um papel fundamental na avaliaþÒo da saúde ambiental de populaþ§es expostas a contaminantes. Este artigo analisa informaþ§es sobre biomarcadores de exposiþÒo e de susceptibilidade, bem como biomarcadores de efeito, que podem ser úteis em estratégias de diagnóstico e de prevenþÒo na exposiþÒo a pesticidas persistentes (organoclorados) e a pesticidas moderadamente persistentes (organofosforados), em um período de alta vulnerabilidade, tal como a gravidez. Ele também revisa vários estudos nos quais tem sido observada correlaþÒo entre biomarcadores de exposiþÒo em matrizes da tríade mÒe-placenta-feto e o impacto no desenvolvimento da gestaþÒo e no crescimento intra-uterino, bem como na funcionalidade do cérebro na infÔncia. Finalmente, este artigo descreve biomarcadores inespecíficos nóveis incluindo biomarcadores epigenéticos, de estresse oxidativo, de disrupþÒo endócrina e de expressÒo gÛnica.(AU)

Biomarkers of susceptibility to chemical carcinogens: the example of non-Hodgkin lymphomas.

BACKGROUND: Genetic susceptibly to suspected chemical and environmental carcinogens may modify the response to exposure. The aim of this review was to explore the issues involved in the study of gene-environment interactions, and to consider the use of susceptibility biomarkers in cancer epidemiology, using non-Hodgkin lymphoma (NHL) as an example. SOURCES OF DATA: PubMed, EMBASE and Web of Science were searched for peer-reviewed articles considering biomarkers of susceptibility to chemical, agricultural and industrial carcinogens in the aetiology of NHL. AREAS OF AGREEMENT: The results suggest a modifying role for genetic susceptibility to a number of occupational and environmental exposures including organochlorines, chlorinated solvents, chlordanes and benzene in the aetiology of NHL. The potential importance of these gene-environment interactions in NHL may help to explain the lack of definitive carcinogens identified to date for this malignancy. AREAS OF CONTROVERSY: Although a large number of genetic variants and gene-environment interactions have been explored for NHL, to date replication is lacking and therefore the findings remain to be validated. GROWING POINTS AND AREAS TIMELY FOR DEVELOPING RESEARCH: These findings highlight the need for novel standardized methodologies in the study of genetic susceptibility to chemical carcinogens.

Research Progress on Biomarkers of Manganism / 环境与健康杂志

Manganese(Mn) is one of the essential trace elements in biologic metabolism.With proper quantity,Mn acts as some enzymes’active groups,reactivators,and participates in the physiological functions of central nervous system.Overdose exposure to Mn in industry may result in occurrence of occupational manganism,which can cause damage of many aspects of the body such as nerve,immunity and reproduction.The aim of present essay is to review the current studies on nerval behavior function and biomarkers of manganism both in China and other countries.