Abstract
Normal serum contains a small molecular weight fraction (Mr 1200) that inhibits the effects of somatomedins/insulin-like growth factors (SM/IGF's) on cartilage segments and epididymal fat pads (Pediatr. Res. 18:1212, 1984). We examined the effects of this somatomedin inhibitory fraction (SmIF) on human skin fibroblast multiplication. The addition of SmIF (10 mlEq/ml) resulted in a significant decrease of total cell numbers (130.000 cells/dish) as compared to control cultures (500.000 cells/dish) after seven days of incubation. This inhibition was partially reversible when SmIF was added to low density cultures, but returned to control values when added during the logarithmic growth phase. SmIF decreased 3H-thymidine incorporation into TCA precipitate in serum and SM/IGF stimulated synchronized human fibroblasts in a dose dependent manner to less than 10 % of control values. Cell numbers, protein content and cell viability remained unchanged. Pulsing with SmIF at different time intervals during serum stimulated DNA synthesis, revealed that it only acted during the first hours after stimulation. The presence of SmIF before stimulation, during late progression or during the thymidine pulse showed no effect. We conclude that SmIF is non-toxic and reversibly inhibits cell multiplication by interfering with competence induction or early progression.
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