Dose–response study of myo-inositol as an inhibitor of lung tumorigenesis induced in A/J mice by benzo[a]pyrene and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone

Dietary myo-inositol is an effective inhibitor of lung tumor induction in mice, but no dose–response studies have been reported. We assessed the ability of various doses of dietary myo-inositol to inhibit lung tumor induction in female A/J mice treated with eight weekly doses of benzo[a]pyrene (BaP) plus 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) (3 μmol of each by gavage), then killed 18 weeks later. In Expt. 1, groups of 20 mice each were treated with myo-inositol at concentrations of 1, 0.5, 0.25, 0.125, 0.0625, 0.03125, and 0% in AIN-93 diet for 1 week prior to, during, and for 1 week after the carcinogen administration period. In Expt. 2, groups of 20 mice each were treated with the same concentrations of myo-inositol in the diet as in Expt. 1, except this diet was administered from 1 week after carcinogen administration until termination. There were no effects of myo-inositol on lung tumor incidence, which was 100% in all groups treated with BaP plus NNK. However, myo-inositol significantly decreased lung tumor multiplicity in both experiments. In Expt. 1, significant reductions of 28.9 and 33.0% were observed at the 1 and 0.5% doses of myo-inositol, but not at the lower doses. In Expt. 2, a significant reduction of 48.4% was observed at the 1% dose. In both Expts. 1 and 2, there was a significant dose trend for inhibition (P<0.0001). No toxicity was observed at any dose. These results firmly establish myo-inositol as a chemopreventive agent against lung tumor induction in A/J mice, at doses that can be envisioned for human use.