Introduction and perspective

Biomarkers of organ injury can be categorized into three types: markers of exposure, markers of effect, and markers of susceptibility.1 Biomarkers of exposure typically are surrogate measures of internal dose or dose to target tissue for a xenobiotic agent. Markers of effect include pathophysiological, cellular, and molecular events that represent the toxic effects of an agent. By contrast, biomarkers of susceptibility are useful in defining which individuals in a population are most likely to respond with toxicity upon exposure to a xenobiotic agent or mixture.

This commentary is a brief exploration of the hypothesis that underlying inflammation is a potentially important determinant of individual susceptibility to toxic agents. To put this in perspective, the reader should bear in mind that there are numerous factors that can contribute to differences among individuals in their sensitivity to xenobiotic agents (Figure 29.1). These include variations in age, gender, xenobiotic metabolism, immuno-logic responses, reserve and repair capacity of tissues, absorption, coexisting disease, coexposure to additional xenobiotic agents, and nutritional status, as well as underlying inflammation. This large number of determinants is sure to coexist and exert influences in concert in any individual. Moreover, many are likely to vary with time, so that a snapshot of an individual's susceptibility, if one could be taken, would not necessarily be indicative of past or future susceptibility. The study of genetic factors that influence these determinants has become an important focus in toxicology in the past several years. An example is the discovery of polymorphisms in metabolic pathways that govern the toxicity of xenobiotic agents. It should be kept in mind, however, that environmental factors have the potential to exert important influences on most of these determinants (Figure 29.1).

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