Inhibition of wool follicle DNA synthesis by mimosine and related 4(1H)-pyridones.

The in vitro incorporation of [3H]thymidine has been examined in thin slices of sheep skin. Most of the radioactivity (88%) was incorporated into the bulb cells of the wool follicles, and the technique is therefore suitable for the study of some aspects of wool follicle DNA synthesis. The effect of mimosine and a number of related 4(1H)-pyridones on [3H]thymidine incorporation into sheep skin slices was examined. Mimosine was shown to inhibit 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-hydroxyl-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 centre, but changes in its polarity have been shown to affect the inhibitory activity. The results suggest that 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.