Effect of Epidermal Polyamine Depletion on the Accumulation of Methylglyoxal Bis(guanylhydrazone) in Mouse Skin

A systemic or topical treatment of mice with alpha-difluoromethylornithine, and irreversible inhibitor of mammalian ornithine decarboxylase, produced a rapid depletion of epidermal putrescine and spermidine. When methylglyoxal bis(guanylhydrazone), another inhibitor of polyamine biosynthesis and a potent antiproliferative agent, was subsequently administered the epidermal concentration of the latter drug rose distinctly higher than without a prior difluoromethyl ornithine treatment. The combined use of these 2 antimetabolites of polyamines also profoundly depressed epidermal DNA synthesis, especially in UV-irradiated skin. A "priming" with difluoromethyl ornithine may therefore offer a means to enhance the epidermal accumulation of otherwise poorly absorbed methylglyoxal bis(guanylhydrazone).