The role of putrescine in cell proliferation of the skin of mice induced by ethylphenylpropiolate

The activities of ornithine and S-adenosylmethionine decarboxylases in the skin of the back of mice increased rapidly after a single topical application of ethylphenylpropiolate (EPP), a potent hyperplastic agent of epidermis, the increase in the former being much greater and more rapid. The tissue concentration of putrescine changed in parallel with change in ornithine decarboxylase activity and was maximal 8 hr after EPP treatment. The spermidine level descreased significantly 4-6 hr after EPP treatment, when putrescine formation from spermidine was accelerated, and increased to 20% more than the normal level at 20 hr. The spermine level did not change within 28 hr after EPP treatment. Administration of dl-α-hydrazino-δ-aminovaleric acid (dl-HAVA), an inhibitor of ornithine decarboxylase, greatly inhibited the increase in putrescine but had little effect on the change in spermidine concentration after EPP treatment. Examination of DNA synthesis and the histological appearance of the skin showed that dl-HAVA also inhibited inducton of cell proliferation by EPP. The inhibition by dl-HAVA was reversed by administration of putrescine, but not cadaverine or 1,7-diaminoheptane. From these results, it is suggested that the rise in the putrescine level induced by EPP is a requisite for subsequent cell proliferation in the skin of mice.