Effects of inhibitors of protein synthesis on structure and function of the crypts of the small intestine

Abstract

Summary Studies conducted with TZA and several different doses of CHM suggest a possible relationship between the proliferation of the intestinal crypt cells and the degree to which their protein biosynthetic capacity is interrupted. An initial inhibition of protein synthesis of less than 80% has either no effect or induces only a partial decrease in the number of dividing cells, while an inhibition in excess of 80% results in a complete abolition of mitotic activity. Similarly, a return of protein synthesis to 20% of control levels appears to be sufficient to support the re-entry of G2 cells into division. Autoradiograms indicate that S phase cells can also continue their progression into the post-synthetic phases of the cell cycle despite a considerable suppression of DNA replication. Despite the marked inhibition of protein and DNA synthesis by CHM, the incorporation of 14C-uridine into RNA was enhanced. This stimulation was more pronounced when protein synthesis had returned to approximately 15–20% of controls. Electron microscopic studies provided some additional insight into the mechanism by which CHM exerts its antimitotic effect and, in addition, revealed that no cytological abnormalities developed in CHM-treated animals. This latter observation indicates that the intestinal crypt cells can tolerate profound aberrations in their metabolic and functional activities without undergoing degenerative changes.