Laboratory of Experimental Pathology
Umberto Saffiotti, M.D., Scientist Emeritus
saffiotti@nih.gov
Umberto Saffiotti was born in Milan, Italy, on January 22, 1928. He entered the University of Milan Medical School in 1944, received the M.D. degree (cum laude) in 1951, and was trained at the Institute of Pathologic Anatomy. Dr. Saffiotti conducted Carcinogenesis research with Dr. P.
Shubik at the Chicago Medical School from 1952 to 1955. He studied the pathogenesis of silicosis and occupational carcinogenesis at the University of Milan (Institutes of Occupational Medicine and of General Pathology) from 1955 to 1960 and received a specialty diploma in occupational medicine in 1957. He became a permanent resident of the United States in 1960 and a U. S. citizen in 1966. From 1960 to 1968, Dr. Saffiotti conducted Carcinogenesis research in the Division of Oncology at the Chicago Medical School, where he became Professor of Oncology. Since 1968 he has been on the staff of the National Cancer Institute, National Institutes of Health, Bethesda, Maryland. As Associate Scientific Director for Carcinogenesis (1968-1976), he directed the expanding research program on chemical and physical carcinogenesis and contributed to establishing criteria for the evaluation of environmental carcinogens. As Chief of the Laboratory of Experimental Pathology (1974-1998), he directed an intramural research program which developed and investigated animal and cellular models chiefly for respiratory and multifactorial carcinogenesis, mechanisms of inhibition by vitamin A, and the role of growth factors in the culture and transformation of epithelial cells. Dr. Saffiotti's research in the Laboratory of Experimental Pathology was devoted to epithelial carcinogenesis, especially respiratory tract carcinogenesis. Experimental models and mechanisms were correlated with the corresponding human pathology. Culture systems for target epithelial cells were developed, especially in serum-free media with selected growth factors, and studied for cellular and molecular mechanisms of transformation. Animal and cellular models were established, first for the induction of bronchogenic and laryngeal carcinoma (mostly squamous cell), and then for peripheral lung carcinomas (mostly alveolar adenocarcinomas). To study the pathogenesis of fibrosis-associated peripheral lung adenocarcinomas, a form of human lung cancer that has become prevalent, an animal model was developed by lung instillation of quartz particles in rats, which induced granulomas with progressive fibrosis (silicosis), adjacent alveolar epithelial proliferation, adenomas and carcinomas, mostly fibrosis-associated adenocarcinomas.
The following interrelated problems were investigated:
Role of species and organ factors in quartz carcinogenesis.
Role of TGF-beta 1 and other factors in preneoplastic and neoplastic proliferation of alveolar cells in the animal models, in human lungs and in alveolar cell cultures.
Animal models and pathology of laryngeal, tracheobronchial, and peripheral lung carcinogenesis.
Mechanisms of neoplastic transformation in cultured BALB/3T3/A31-1-1 mouse embryo cells and in epithelial cells, including mouse epidermal keratinocytes and rat lung alveolar epithelial cells, with serum-free or low-serum media.
Physico-chemical mechanisms of biological interactions of the crystalline surface of quartz and other minerals, leading to DNA binding, DNA damage, generation of free radicals, mutation and transformation.
Identification of selective inhibitors and modifiers of quartz-induced cytotoxicity, DNA damage and/or transformation, and underlying mechanisms.
Dr Saffiotti is continuing his research in collaboration with several groups of investigators; his current interests are in the mechanisms of biological activity, especially carcinogenesis, determined by physicochemical characteristics of particulate mineral surfaces and by their combined role with the oncogenic virus SV40.
Dr Saffiotti is currently Scientist Emeritus in the Division of Basic Science, NCI, NIH, and also Adjunct Professor of Environmental and Occupational Heatlth at the George Washington University School of Public Health and Health Services, Washington, D.C.
Dr. Saffiotti has authored or co-authored about 190 publications and 30 committee or group reports.