Relationship of Cell Growth Behavior in Vitro to Tumorigenicity in Athymic Nude Mice1

For both theoretical and practical considerations, it would be useful to understand the relationship between growth behavior of tissue culture cell lines and growth control of normal animal tissues in vivo. A review of pre vious attempts to determine this relationship suggested to us that 1 source of the discrepancies was the assay for tumonigenicity. After prolonged growth in the laboratory, animal cell lines can acquire new or modified surface anti gens as a result of viral infections, mutations, or epigenetic changes. These altered surface antigens can mask the tu monigenicity, even of cell lines derived from inbred animal hosts by provoking an immune response. Measurements of cellular tumonigenicity are probably least ambiguous when conducted in immunologically suppressed animals. Additionally, many, if not most, studies on transformation and comparative tumomigenicity have used secondary em bryonic cell strains and cell lines such as 3T3 and BHK as the “ normal― controls. The bulk of human neoplasms are of epithelial origin. Therefore, it would be desirable to conduct comparative tumonigenicity studies with cell lines of epithe hal origin to determine whether principles established with embryonic cell strains and †̃ †̃fibroblast-like' †̃ cell lines can be extended. In a previous communication (18), our laboratory pre sented evidence that the congenitally athymic nude mouse is a reliable host for assessing the tumonigenic potential of both animal and human cell lines. The tumonigenic poten tial of fibroblast-like and epithelioid cell lines derived from both normal and neoplastic tissue was determined. To de termine the extent to which growth-regulatory behavior commonly observed in vitro such as serum requirement, anchorage requirement, density-dependent growth inhibi tion, and contact inhibition of growth are relevant to tumor formation in animals, we have correlated these properties with the tumomigenic potential in nude mice. The results of these studies are presented below.