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 (B aP) plus4-(methylnitrosamino)- 1-(3-pyridyl)-1-butanone (NNK) (3 mu mol 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 AlN-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 myoinositol 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, Inyo-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 mono-inositol as a chemopreventive agent against lung tumor induction in A/J mice, at doses that can be envisioned for human use. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.