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 m ice, but no dose-response studies have been reported. We assessed the abili ty 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 ea ch by gavage), then killed 18 weeks later. In Expt. 1, groups of 20 mice ea ch 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 fo r 1 week after the carcinogen administration period. In Expt. 2, groups of 20 mice each were treated with the same concentrations of myoinositol in th e diet as in Expt. 1, except this diet was administered from 1 week after c arcinogen administration until termination. There were no effects of myo-in ositol on lung tumor incidence, which was 100% in all groups treated with B aP plus NNK. However, Inyo-inositol significantly decreased lung tumor mult iplicity in both experiments. In Expt. 1, significant reductions of 28.9 an d 33.0% were observed at the 1 and 0.5% doses of myo-inositol, but not at t he lower doses. In Expt. 2, a significant reduction of 48.4% was observed a t the 1% dose. In both Expts. 1 and 2, there was a significant dose trend f or inhibition (P < 0.0001). No toxicity was observed at any dose. These res ults 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.