Assessing health effects of environmental contaminants by molecular markers. Studies on methylmercury and polychlorinated biphenyls as examples of translational research in environmental toxicology.
Evaluating the human effects of combinations of neurotoxicants is extremely difficult. Parallel studies correlating exposure parameters and "surrogate" indicators of neural cell function may represent a promising strategy. Molecular markers such as cholinergic muscarinic receptors (MRs) and monoamine oxidase activity (MAO-B) are expressed not only in brain but also in peripheral blood cells. Measurements of MRs and MAO-B in these easily accessible matrices can provide valuable information on early sub-clinical effects of drugs and chemicals in the CNS. In this paper, examples of application of lymphocyte-MRs and platelet-MAO-B as surrogate markers of CNS function in humans are described. They include (i) neuroepidemiological studies examining 7-year-old members of a birth-cohort at the Faroe-Islands prenatally exposed to elevated concentrations of methylmercury (MeHg) and polychlorinated biphenyls; (ii) clinical investigations in a series of unmedicated children with Attention-Deficit/Hyperactivity Disorder (ADHD). The neurochemical markers were examined in association with exposure indicators and neuropsychological tests (Faroe Islands Study) or with specific disease symptoms (ADHD children). Studies of this type have produced valuable information on subclinical responses to low/moderate perinatal exposures to MeHg and/or PCBs, and in addition further supported the applicability of these biomarkers in children with subtle neuropsychiatric disorders. Additional studies investigated the ability of MeHg and/or PCBs to modify the expression of genes codifying for the MR subtypes in rat offspring cerebellum at distinct developmental stages. The results demonstrated persistent gender- and age-related differences in MR density and their associated gene expression pathways. Studies on pathways and metabolic networks involved in developmental toxicity may contribute to elucidate the mode of action of environmental pollutant mixtures and also considerably impact on the risk assessment process.
Coccini
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Salvatore Maugeri Foundation IRCCS, Toxicology Division, Pavia, Italy. teresa.coccini@fsm.it
Roda
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Sarigiannis
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Manzo
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D000818:Animals; D015415:Biomarkers; D054750:Ecotoxicology; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008297:Male; D008767:Methylmercury Compounds / Q000633:toxicity*; D008995:Monoamine Oxidase / Q000187:drug effects / Q000502:physiology; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D057170:Translational Research, Biomedical
D015415:Biomarkers; D004785:Environmental Pollutants; D008767:Methylmercury Compounds; D011976:Receptors, Muscarinic; D011078:Polychlorinated Biphenyls; D008995:Monoamine Oxidase