This program project supports a variety of individual research efforts designed to investigate the interaction between radiation and chemotherapeutic agents at the molecular, cellular, tissue, and organismal levels. There are close interrelationships between various research projects and with other departments in the Harvard Medical School area. These include the Departments of Neurobiology, Pharmacology, Nuclear Medicine, and Physiology (Harvard School of Public Health). Less formal relationships exist withthe Departments of Medical Oncology, Pediatric Oncology, Pharmacology, and Cell Biology at the Sidney Farber Cancer Institute. The research supported by this program project has important relevance to cancer treatment because of its concentration on damage interaction between radiation and chemotherapeutic agents and the development of the base for the use of hypoxic cell sensitizers during radiotherapy. The specific aims of this program project include support of young investigators, research associates, and to foster inter-departmental collaboration. The research includes studies on the genetic control mechanisms of drug resistance in mammalian cells, the radiation response of drug resistant cells, the long-term effects of radiation and chemotherapeutic agents on bone marrow stem cell function, the development of techniques for labeling of specific agents with radionuclides, the cell biology of hormone receptor relationships in gene activation, identification of cell surface properties which are important in the response to teratogens and carcinogens, repair of slow and rapid radiation damage in mammalian cells, and studies on the toxicity of metabolic products resulting from the incubation of hypoxic mammalian cells inthe presence of misonidazole.