We tested the ability of avicins, a family of triterpenoid saponins obtained from Acacia victoriae (Bentham) (Leguminosae: Mimosoideae), to inhibit chemically induced mouse skin carcinogenesis. Varying doses of avicins were applied to shaved dorsal skin of SENCAR mice 15 min before application of 100 nmol of 7,12-dimethylbenz[a]anthracene (DMBA) twice a week for 4 weeks (complete carcinogenesis model). The dorsal skin of a second group of mice was treated with one dose of 10 nmol of DMBA. Avicins were then applied 15 min before repetitive doses of 2 g of phorbol 12-tetradecanoate 13-acetate (TPA) twice a week for 8 weeks (initiation͞promotion model). At 12 weeks, avicins produced a 70% decrease in the number of mice with papillomas and a greater than 90% reduction in the number of papillomas per mouse in both protocols. We also observed a 62% and 74% reduction by avicins in H-ras mutations at codon 61 in the DMBA and DMBA͞TPA models, respectively, as well as a significant inhibition of the modified DNA base formation (8-OH-dG) in both protocols. Marked suppression of aneuploidy occurred with treatment at 16 weeks in the initiation͞promotion experiment. These findings, when combined with the proapoptotic property of these compounds and their ability to inhibit hydrogen peroxide (H 2O2) generation, nuclear factor-B (NF-B) activation, and inducible nitric oxide synthase (iNOS) induction reported elsewhere, suggest that avicins could prove exciting in reducing oxidative and nitrosative stress and thereby suppressing the development of human skin cancer and other epithelial malignancies. T riterpenoid saponins, which are present in some plants and marine animals, have been suggested to have anticarcinogenic properties (1). We have recently reported the characterization of an extracted mixture of novel triterpenoid saponins (designated Fraction 35; F035) from above-ground plant parts of Acacia victoriae (Bentham) (Leguminosae: Mimosoideae; ref. 2). We have also extracted a seedpod sample of A. victoriae to obtain a comparable triterpenoid saponin mixture (F094). Both extracts (F035 and F094) contain multiple individual triterpene glycoside molecular species. Pure compounds were then fractionated from F094 and designated avicins D and G (3). All data comparing the in vitro activity of F035 and F094 with avicins D and G demonstrate consistently that they share similar properties in cancer cell lines. HPLC analysis indicated similar chemical profiles for both F035 and F094, but relative amounts of triterpenes varied. For example, avicin G (lipophilic region) was more abundant in F035, and avicin D (polar region) was more abundant in F094.In the present study, we use the murine skin carcinogenesis model, an ideal system for identifying critical target genes for the action of chemical or physical carcinogens. Skin carcinogenesis in mice can be accomplished by using either complete carcinogenesis or multistage protocols (2). Complete carcinogenesis protocols involve the administration of a single dose or repeated applicatio...

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