Simulation of Genetic Mucopolysaccharidoses in Normal Human Fibroblasts by Alteration of pH of the Medium

Abstract

Catabolism of sulfated mucopolysaccharide by normal human fibroblasts in culture is progressively inhibited as the pH of the growth medium is raised from 6.8 to 8.0. The final cell density increases with the change in pH. The capacity to degrade mucopolysaccharide is rapidly restored by lowering the pH, and this reactivation does not require protein synthesis. Such pH dependence is not observed in cells from patients with genetic impairment of mucopolysaccharide degradation, such as the Hurler or Hunter syndromes. These results may have relevance not only to studies of mucopolysaccharide metabolism in cell culture, but also to the use of metachromasia as a genetic marker and to the observation that normal fibroblasts are released from contact inhibition of growth as the pH of the growth medium is raised.