Methodologic issues, theoretical considerations, and design criteria for experimental animal and cell culture...

This article provides background information that is important when evaluating the relevance to humans of particular animal or in vitro experiments designed to assess the relations between fatty acids and cancer. Considerations in designing carcinogenesis studies to assess the relation between dietary fatty acids and human cancer include selection of the animal model and design of the experimental diets. Animal carcinogenesis models are generally best for evaluating the early phases of cancer development: the initiation and promotion of cancer. Transplantation 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 biology 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 relative to the different phases of tumor growth and metastasis. Studies in cultured cells have been particularly useful for assessing the mechanisms by which fatty acids affect cancer. Considerations in designing studies with cultured cells include selection of the cell line, cell culture conditions, selection of biological endpoints that are relevant to human cancer, and in vivo confirmation of the mechanisms observed in vitro. Design considerations for each of these experimental approaches are discussed and the contributions of each approach are summarized.