Exposure of cells to ultraviolet light, ionizing radiation and certain chemicals can lead to cell death, mutation or malignant transformation. All these agents produce damage to the genetic material. Ionizing radiation and certain chemicals, mutagens and carcinogens, are of particular importance to the Health Sciences since they are at the same time dangerous potential "pollutants" of our environment and important tools in the treatment of many diseases, in particular, of cancer. The major aim in our program is to identify and characterize DNA excision repair pathways in normal and diseased human cells. The excision of damage produced in DNA by ultraviolet light, ionizing radiation and the chemical carcinogens ethylnitrosourea and benz(a)pyrene is being investigated. An "open system" using whole cell sonicates or nuclear preparations from cultured human skin fibroblasts and exogenous, damaged DNA substrates is being used in part of our experiments. The excision capacity of preparations from normal cells are compared to preparations from Fanconi's Anemia and Xeroderma pigmentosum cells. Fanconi's Anemia and Xeroderma pigmentosum are autosomal recessive diseases in man with increased frequencies for the development of cancer. Excision competition studies are being carried out with DNA substrates containing different classes of DNA lesions. The goal in these studies is to distinguish different excision pathways and to derive a functionally meaningful classification of DNA base damage. The excision of DNA-alkylation damage produced by ethylnitrosourea will also be investigated in human lymphocytes (whole cells). BIBLIOGRAPHIC REFERENCES: M. Mattern and P. Cerutti - Age-dependent Excision Repair of Damaged Thymine from Gamma-irradiated DNA by Isolated Nuclei from Human Fibroblasts. Nature 254, 450 (1975). P. Cerutti - Repairable Damage in DNA: Overview in "Molecular Mechanisms for the Repair of DNA" Part A, p. 3 (eds. P. Hanawalt and R. Setlow) Plenum Press, New York (1975).