Studies on Down's syndrome in tissue culture. I. Growth rates and protein contents of fibroblast cultures.

Abstract

AbstractSkin fibroblast cultures from six patients with Down's syndrome (Trisomy 21) were compared with four in vitro age‐matched normal fibroblast cultures. Growth rates were calculated from increases in cell number and total protein during exponential growth, early in culture lifetime (less than 20 doublings). The Down's syndrome (D.S.) cultures had an average population doubling time of 35.6 ± 1.1 hours and average mass doubling time of 38.6 ± 3.2 hours, significantly lower (p<0.005) than the corresponding normal culture values of 23.0 ± 0.7 hours, and 23.3 ± 1.9 hours. D. S. Cells also contained 4.46 ± 0.19 ± 10−4 μg protein/cell as compared to 3.06 ± 0.13 × 10−4 μg/cell (p<0.001) for normal fibroblasts.Similar in vitro observations of increased doubling time and protein content have been reported in normal fibroblasts from older donors, and from individuals with premature aging syndromes, as well as in normal fibroblasts near the end of their in vitro lifetime. The present results, obtained from cultures young in vitro, may therefore suggest that D.S. fibroblast cultures age prematurely. This hypothesis is consistent with clinical manifestations of premature aging in D.S. patients and points to a defect in growth regulation, both in vivo and in vitro, resulting from an extra copy of chromosome 21.