Comparison of the effects of bilobol and 12-O-tetradecanoylphorbol-13-acetate on skin, and test of tumor promoting potential of bilobol in CD-1 mice.

Abstract

Bilobol, isolated from ginkgo fruit pulp, has been noted to be a strong skin irritant like 12-O-tetradecanoylphorbol-13-acetate (TPA), a tumor-promoter in the skin. A comparative investigation of morphological changes induced by bilobol and TPA induced in the skin of CD-1 mice, and an assessment of the skin tumor promoting potential of bilobol were therefore performed. In experiment I, mice received a single application of 2.5, 50 or 1000 micrograms of bilobol, or 0.1 or 2.5 micrograms of TPA on the right ear. The 50 or 1000 micrograms bilobol and 2.5 micrograms TPA doses caused ear redness, epidermal thickening and inflammatory infiltration. The dose of 2.5 micrograms of TPA, which is usually used as tumor promoter in skin carcinogenesis, was equivalent to 50 micrograms of bilobol in irritant effect. Thus, 50 micrograms of bilobol was used for the promotion testing (experiment II) in CD-1 mice initiated with 100 micrograms of 7, 12-dimethylbenz[a]anthracene (DMBA). Treatment with either 10 or 50 micrograms bilobol twice a week for 30 weeks did not result in any tumor development, thus suggesting that bilobol is not a complete promoter of skin carcinogenesis, despite generation of inflammation.