Carcinogen-DNA and Protein Adducts as Intermediate Biomarkers for Human Chemoprotection Trials
Our rapidly expanding understanding of the progressive processes of carcinogenesis provides opportunities for the identification of molecular biological markers reflecting events from carcinogen exposure through clinical cancer. A joint committee of the National Academy of Sciences and the National Research Council1 has developed a useful conceptual framework for these processes and is shown in an adapted form in Figure 1. This model groups molecular biomarkers into sets reflective of internal dose, biologically effective dose (dose to critical macromolecules), early biological effect, altered structure/function, and clinical disease as well as those reflecting underlying susceptibility factors. In more general terms, molecular biological markers can be considered to fall into broad categories of markers of exposure, biological effect, and susceptibility. Markers of exposure reflect exposure levels to toxic agents, markers of effect indicate a biological response to an exposure, and markers of susceptibility provide information about the inherent sensitivity of an individual to a toxic agent. By definition some of these markers are chemical-agent specific, such as a carcinogen-DNA or protein adduct, while others are biological-process specific, such as the altered expression of an oncogene protein.
KeywordsLiver Cancer Protein Adduct Intermediate Endpoint Aflatoxin Exposure Chemoprotective Agent
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