Inhibition of Wool Follicle DNA Synthesis by Mimosine and Related 4(1H)-Pyridones

Abstract

The in vitro incorporation of [3H]thymidine was examined in thin slices of sheep skin. Since most of the radioactivity (88%) was incorporated into the bulb cells of the wool follicles, the technique is suitable for the study of some aspects of wool follicle DNA synthesis. The effect of mimosine, [a possible chemical deficiency agent] and a number of related 4(1H)-pyridones on [3H]thymidine incorporation into sheep skin slices was examined. Mimosine inhibited the incorporation at a concentration of 0.2 mM. At this concentration, the incorporation of [3H]uridine or [14C]leucine was not affected. The inhibition of [3H]thymidine incorporation was time dependent, 2 h of incubation being required for maximal inhibition of DNA synthesis, and was readily reversible by removal of mimosine from the incubation medium. The 3-hydroxy-4-oxo function of the pyridone ring appears to be directly involved in DNA synthesis inhibition. The amino acid side chain is not a toxophoric center, but changes in its polarity affected the inhibitory activity. The primary action of mimosine on the inhibition of wool biosynthesis in vivo is the inhibition of follicle bulb cell DNA synthesis and consequently of cell division.