A multi-disciplinary program for pre-doctoral and postdoctoral training in molecular toxicology is proposed, with emphasis on environmental agents. Pre-doctoral training candidates will be trained within four existing basic science curricula (Biochemistry, Molecular Genetics, Physiology and Pharmacology, and Cancer Biology) in a unique program with modified course and other requirements. This program is poised for initiation in the sense that most of the sixteen mentors are experienced in the training of pre-doctoral candidates and/or postdoctoral fellows to function independently as investigators in mechanistic toxicology. Indeed, many are currently advisors for one or more individuals. The purpose of this training grant is to provide support for a coordinated and cohesive training program that will be supervised and highly interactive. The program will provide state-of-the art training in molecular toxicologic sciences, with primary focus in two areas: 1) understanding molecular mechanisms of toxic injury at the cellular level (with special emphasis on DNA damage); and 2) defining the functionality, regulation, and disease relevance of pathways of cellular defense against toxic insult. A closely related ancillary goal will be to train researchers in the investigation of the mechanistic consequences of interindividual differences in genetic predisposition to toxic injury. The faculty included as mentors in this training program are all experienced independent investigators of mechanisms of toxicologic damage, pathways of cellular defense, and/or genetic polymorphisms that may alter individual susceptibility to chemical-induced disease. The program is designed to provide training that will prepare future investigators with a broad foundation of basic science knowledge, a solid grasp of the relevant scientific literature, and a versatile palette of molecular biologic research skills for application to toxicologic questions. This program will fill a need for investigators trained in toxicologic science at the molecular mechanistic level, focusing on the roles played by specific genes or sets of genes. The investigators will encourage research on gene-environment interactions, with particular emphasis on the functional significance of genetic polymorphisms that are relevant to environmental toxicology.