Relationship between chromosomal changes and alterations in the behaviour of a strain of human synovial cells during its life history in vitro.

The eventual occurrence of gross aberrations in the number and pattern of chromosomes is one o the main objections to the use of cell cultures in the study of physiology and disease. Such aberrations are essential features of the permanent cell lines such as HeLa, and accompany the phenomenon of "transformation", in which radical changes occur in cell structure, growth, and secretory functions. Transformation to "established" cell lines is commonly observed in cells from healthy rat and mouse tissues growing in vitro (Levan and Biesele, 1958; Rothfels and Parker, 1959). Several examples have been recorded of similar transformations in cells propagated from human neoplasms (Gey, Coffman, and Kubicek, 1952; Fjelde, 1955; Berman, Stulberg, and Ruddle, 1957). In contrast, transformation rarely occurs in cells from "normal" human tissues and these can often be grown for considerable periods in continuous serial cultivation without serious deviations from the euploid state (Puck, Cieciura, and Robinson, 1958; Hayflick and Moorhead, 1961; Ferguson and Wansbrough, 1962). However, Saksela and Moorhead (1963) found that minor aneuploid changes occurred late in the life of the human strains W126 and W138. These chromosomal alterations could be clearly correlated with changes in the morphology and rates of growth of the cells. Hsu, Pomerat, and Moorhead (1957) first reported chromosomal studies on normal human synovial cells in culture. They found early aneuploid changes in a "strain" of cells propagated from synovial explants. Castor (1960) briefly described similar chromosomal alterations in explanted human synovial cells. Ferguson found normal chromosome counits and karyotypes in three synovial strains studied after 58, 71, and 106 days respectively (Fraser and McCall, 1965). The inference that synovial cells might be intrinsically unstable in vitro has not received further investigation. The present paper reports a study designed to contribute more detailed information on chromosomal and behavioural changes in human synovial cells in vitro.