Increased phosphatidylinositol synthesis in rat embryo fibroblasts after growth stimulation and its inhibition by δ-hexachlorocyclohexane

Abstract

When resting rat embryo fibroblasts are stimulated to grow, a substantial increase in phosphatidylinositol synthesis can be observed. This increase cannot be explained by increased glucose uptake or glycolysis. δ-Hexachlorocyclohexane having the same configuration as myo-inositol, inhibits phosphatidylinositol synthesis as well as DNA synthesis and mitosis, but has no effect on phosphatidyl choline synthesis. When δ-hexachlorocyclohexane is added to fibroblast cultures during the first hours after stimulation, a delay of DNA synthesis and mitosis compared to uninhibited cultures can be observed. Since δ-hexachlorocyclohexane also inhibits the uptake of nucleotides, hexoses and amino acids, it is suggested that phosphatidylinositol is necessary for the proper functioning of those receptors and carriers which are an essential part of the early cellular processes after growth stimulation, and this role of phosphatidylinositol may explain its increased turnover in growing cells. The increased phosphatidylinositol synthesis could not be associated to one of the subcellular fractions. When cells were labeled with [ 32P]orthophosphate during the first 10 min after growth stimulation and were subsequently separated into cellular fractions such as nuclei, mitochondria, plasma membranes, and microsomes, no significant differences in radioactivity of phosphatidylinositol among those fractions could be observed.