Relationship of phenotypic expression of blood group H to changes in growth kinetics of cultured primary and transformed epithelioid cells.

Population studies of continuously cultured primary amnion cells from appropriate donors and of HeLa cells have established that the H- cell behaves as a stem cell which commonly divides into a like cell and a differentiated H+ type. Exfoliated H+ cells, anucleate or with small or pyknotic nuclei and impaired membrane function, constitute the terminal cell in this process. Stem and differentiated populations have been identified and enumerated a) during the phase of exponential growth in monolayer culture, b) in the course of serial transfers of established and primary cultures, c) in chemically synchronized cells and d) in nutritionally deprived cells. Under the experimental conditions, the rate of phenotypic expression of group H was essentially the same in primary amnion cells from group O donors and in HeLa cells during the phase of exponential growth. The quantitative experiments on H+/H- cell populations suggested that the phenotypic expression of blood group H was adversely affected by altered cell growth which came about by limiting the potential of H- stem cells for differentiation. This occurred following multiple passages of primary cell cultures, or under conditions of nutritional inadequacy in HeLa cells. Studies on chemically synchronized cells indicated that following exposure to excessive thymidine, the predominant cell doubling pattern was reflected as mixed H+/H- progeny. Limitations imposed upon the ability of stem cells to differentiate are probably expressed either as slowly cycling, noncycling or nonviable cells and compensation by surviving stem cells may be provided for by changes in the cell doubling pattern. Since L-fucose is the immunodeterminant sugar for blood group H, it is proposed that a portion of the cellular DNA codes for a fucosyl transferase enzyme responsible for attaching this sugar to a membrane acceptor molecule. Disturbances of cell growth may interrupt this pathway at one or more points.