Inhibition of skin cancer by IP6 in vivo: Initiation-promotion model

A two-stage mouse skin carcinogenesis model was used to examine the effects of IP6 on initiation and promotion phases of tumorigenesis. Seven week old ICR female mice were divided into 6 groups, each consisting of 20 animals. Initiation was performed by a single application of the carcinogen 7,12-di methyl benz(a)anthracene (DMBA) (50 mu g) to the back skin. Three weeks lat er, local application of the promoter TPA was started (2.5 mu g, 2 x/week) and continued up to the end of the experiment (22 weeks). Mice were also ad ministered 2% IP6 in drinking water over the entire duration of the experim ent, or during the initiation (initial 3 weeks) or promotion (final 19 week s) periods only. The animals consuming IP6 during the initiation stage show ed an approximately 50% reduction in the mean number of papillomas per anim al, as well as in the number of tumor bearing mice. However, no such inhibi tion was observed when IP6 was given during the tumor promotion stage. In a separate experiment the effects of IP6 on epithelial cell growth were asse ssed by BrdU labeling at several time points. Statistically significant inh ibition of cell proliferation was observed during the initiation stage (one week after DMBA treatment) in the group given IP6. No inhibition was evide nt during the promotion stage.