Introduction to Molecular Toxicology

Molecular toxicology is an area of specialization within the field of toxicology concerned with unraveling the molecular basis of the biological response to harmful chemical, physical, or biological agents. Historically, the emphasis has been on chemical and physical agents. More recently, concerns with biological warfare and food contamination have heightened the interest of toxicologists in biological toxins. The field first evolved from efforts to add resolution to the study of mechanisms of toxicity and its connection to pathogenesis by taking advantage of the tools made available by the burgeoning field of molecular biology. Indeed, such efforts reflect the maturation of toxicology as a science dating back thousands of years. Toxicology is one of the oldest intellectual endeavors of mankind. Dating back to 3000 BC, emerging populations quickly recognized the importance of understanding the effects of poisons in living systems and their major role in self-preservation and death. The routine use of poisons as aids to improve quality of life or as means to dispose of the enemy was swiftly embraced by early civilizations. The use of poisons in the management of illness paved the way for major developments in the field of medicine. In more recent times, the evolution of toxicology as a discipline has been marked by interdigitation with the fields of biochemistry, cell biology, genetics, molecular biology, pathology, and pharmacology. Such interactions have led to fuzzy demarcations among these disciplines and the expansion and refinement of multiple areas of subspecialization within these respective fields of scientific endeavor. In modern times, the science of toxicology has had significant penetration in the society. Toxicology is practiced as a profession in the academic, government, and corporate sectors. Not surprisingly, toxicology as a distinct scientific discipline has expanded rapidly, due in large measure to the proliferation of chemicals being produced and deployed, the dependence of modern society on drugs and chemicals, and increased awareness of the risks that chemical, physical, and biological agents pose to living systems and their environment. The maturation of toxicology as a science has seen the integration of molecular biology as a means to resolve the complexity of the toxic response at the molecular level. This has led to the creation of molecular and cellular toxicology as a distinct subdiscipline within the field of toxicology and formal recognition of this status within the organizational structure of universities, government agencies, and units within the corporate sector. This trend was recognized by the Society of Toxicology, the largest professional organization of toxicologists in the world, with the creation of a specialty section focusing in molecular biology. Indeed, molecular biology has significantly influenced the evolution of toxicology into a molecular science. How do genetic differences lead to variation in human responses to drugs and chemicals? What are the critical molecular targets of toxicity that mediate class-specific responses to toxic injury? What is the molecular basis of pathogenesis mediated by toxic injury? These are some of the questions tackled by the molecular toxicologist. A key to answering these and related questions are the molecular probes and tools that continue to emerge and that are discussed in this volume. As such, the molecular toxicologist has forced a paradigm shift in how toxicology is performed, moving away from high-dose toxicity studies to lower dose exposures that replicate conditions of the human experience. Recently, advances in high-throughput and whole-genome assays have had tremendous impact, forcing the research community to rethink some of its reductionist approaches and to adopt a more global understanding of the complex biology of health and disease. Molecular toxicology has continued to advance at a fast pace. Its maturation is the major reason that a separate volume focusing on molecular toxicology is now part of every major compendium of the field of toxicology. Many of the useful elements highlighted in the previous edition of this introductory chapter have been retained to ensure that the readers at all levels appreciate the unique features and nuances of the field.