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 IP 6 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-dimethyl benz(a)anthracene (DMBA) (50 μg) to the back skin. Three weeks later, local application of the promoter TPA was started (2.5 μg, 2×/week) and continued up to the end of the experiment (22 weeks). Mice were also administered 2% IP 6 in drinking water over the entire duration of the experiment, or during the initiation (initial 3 weeks) or promotion (final 19 weeks) periods only. The animals consuming IP 6 during the initiation stage showed an approximately 50% reduction in the mean number of papillomas per animal, as well as in the number of tumor bearing mice. However, no such inhibition was observed when IP 6 was given during the tumor promotion stage. In a separate experiment the effects of IP 6 on epithelial cell growth were assessed by BrdU labeling at several time points. Statistically significant inhibition of cell proliferation was observed during the initiation stage (one week after DMBA observed during the initiation stage (one week after DMBA treatment) in the group given IP 6 . No inhibition was evident during the promotion stage.