METHODOLOGIC ISSUES, THEORETICAL CONSIDERATIONS, AND DESIGN CRITERIA FOR EXPERIMENTAL ANIMAL AND CELL-CULTURE EXPERIMENTS

This article provides background information that is important when ev aluating the relevance to humans of particular animal or in vitro expe riments designed to assess the relations between fatty acids and cance r. Considerations in designing carcinogenesis studies to assess the re lation between dietary fatty acids and human cancer include selection of the animal model and design of the experimental diets. Animal carci nogenesis models are generally best for evaluating the early phases of cancer development: the initiation and promotion of cancer. Transplan tation protocols have been developed for evaluating the effect of diet on the growth and metastasis of partially or fully transformed cells. The variables that are important in such models are the origin and bi ology of the cell line, the animal host used for the implantation, the site of transplantation, whether the primary tumor is excised after a period of time to allow for metastasis, and when the diets are fed re lative to the different phases of tumor growth and metastasis. Studies in cultured cells have been particularly useful for assessing the mec hanisms by which fatty acids affect cancer. Considerations in designin g studies with cultured cells include selection of the cell line, cell culture conditions, selection of biological endpoints that are releva nt to human cancer, and in vivo confirmation of the mechanisms observe d in vitro. Design considerations for each of these experimental appro aches are discussed and the contributions of each approach an summariz ed.