Biomarker research in neurotoxicology: the role of mechanistic studies to bridge the gap between the laboratory and epidemiological investigations.

Abstract

There is an increasing interest in the development and validation of biomarkers for use in biochemical/molecular epidemiological studies. Though the area of neurotoxicology has received much attention in the past several years, it still lags behind with regard to the development of biomarkers, particularly those of health effects and susceptibility. This review discusses several aspects of biomarker research as it relates to neurotoxic compounds and focuses on selected agents (organophosphorus insecticides, styrene, n-hexane, carbon disulfide, acrylamide), which have been the subject of a number of investigations in animals and humans. While traditional biomonitoring approaches and novel techniques (e.g., hemoglobin adducts) provide several measurements for monitoring exposure to neurotoxic chemicals, potential markers of genetic susceptibility have been seldom investigated in a neurotoxicology context. Furthermore, the complexity of the nervous system, together with the multiplicity of end points and the limited knowledge of the exact mechanism(s) of action of neurotoxicants, has led to only limited advancements in the development of biomarkers for neurotoxic effects. Significant progress in this area will depend upon an increased understanding of the cellular, biochemical, and molecular targets directly involved in neurotoxicity.

Protein adducts as biomarkers of exposure to organophosphorus compounds

“…Proteins are modified only by the active pesticide or nerve agent and their breakdown products will not react with target biomarker proteins. Proteins from the blood compartment fit the criteria for useful biomarkers: they are biological proteins that can be analyzed to provide key information about the health of the subject and the origin of the exposure, they can be analyzed, they have relatively long half-lives, they are also relatively inexpensive to assay, and they provide unequivocal information about the nature and level of OP exposure (Costa, 1996; Henderson et al 1989; Kim et al 2010). Various blood proteins serve as biomarkers of exposure, effect or susceptibility.…”

“…Although highly sensitive and precise, MS approaches do have some drawbacks. The measurements can be difficult and time consuming (Costa, 1996). They also need to be carried out in a stable laboratory-based environment by well-trained technicians.…”

Proteomic analysis of adducted butyrylcholinesterase for biomonitoring organophosphorus exposures

“…The term biomarker refers to biological substances that are indicators of exposure or disease [15], and that can be measured by laboratory techniques [16]. There is an increasing interest in identifying and characterizing new biomarkers for a better health assessment.…”

“…Part of the original OP structure is released during the reaction of the OP with the active-site serine and another part during the aging process; therefore MS may provide ambiguous or limited identification of the specific OP of exposure. LC–MS/MS also has some limitations or disadvantages, such as being time consuming, costly, limited by reactivation, and requiring well-trained personnel [16, 23]. …”

Mass Casualties and Health Care Following the Release of Toxic Chemicals or Radioactive Material—Contribution of Modern Biotechnology

“…Because the life span of red blood cells is comparatively long (approximately 4 months), binding to hemoglobin is considered a good biomarker to measure repeated exposure or exposure that occurred weeks or even months before sampling [25]. …”