ABSTRACT

Postgenomic technologies, including those used to analyze genomic, transcriptomic, proteomic, metabonomic, and other “omic” targets, have made it possible to define molecular physiology in exquisite detail, when tissues are accessible for sampling. However, many target tissues are not accessible for human experimental or epidemiological studies, or clinical evaluations, creating the need for surrogates that afford insight into exposures and effects in such tissues. A “surrogate” can be

defined simply as “one that takes the place of another.” In surrogate tissue analysis (STA), one tissue takes the place of another. More specifically, an accessible tissue takes the place of an inaccessible target tissue. For example, one might examine a patient’s peripheral blood lymphocytes (PBLs) to determine whether that person has suboptimal endometrial receptivity (Chapter 8), has suffered from neurological damage (Chapter 3), has developed a nonlymphatic neoplasm (Chapter 4), or has been exposed to a toxicant (Chapter 5). An alternative STA paradigm is to measure or analyze parts or products of a target tissue that originate from the target, but are collected or measured distal to it, in the surrogate tissue. For example, it is possible to isolate and analyze sperm from semen and use the data to help understand molecular events occurring in the testis (Chapter 6). In a similar manner, peripheral blood can be a source of circulating tumor cells that have detached or have been shed from their parent neoplasm. These can be isolated and used as a source of information about the original neoplasm (Chapters 13 and 14). In other cases soluble proteins, metabolites, or lipids are secreted or excreted from target tissues, and these can be detected and measured in fluids such as blood (Chapters 7, 11, and 12), cerebrospinal fluid (Chapter 11), nipple aspirate (Chapter 9), seminal fluid, milk, saliva, and urine. Drugs, drug metabolites, and toxicants can also be detected in such fluids (Chapters 10 and 11).