Connecting Molecular and Cellular Models with the Corresponding Events in Tissues and Organs: In vitro/in vivo Comparisons in Respiratory Tract Carcinogenesis,
NATIONAL CANCER INST BETHESDA MD LAB OF PATHOLOGY
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Toxic and particularly carcinogenic effects of chemical and physical agents are usually studied on a very restricted number of in vitro models. The development of a sequential series of model systems that would link human pathology at main target sites with the corresponding experimental models in whole animals or in cultured target tissues and cells for the study of cellular and molecular mechanisms is discussed. Particular emphasis was given to the development of models for respiratory carcinogenesis. Progress has been made in the development of sequential models in vivo and in vitro for the same target cell types that are known as cells of origin of induced neoplasia in human pathology. Pathogenetic mechanisms can thus be comparatively investigated in relation to human pathology, including metabolic activation and binding of carcinogens, biochemical effects on cell regulatory pathways, biochemical and morphologic markers, genetic damage and repair, the activation of transforming or permissive genes, the role of cell death, and the role of cell-cell communication signals.