Evaluation of butylated hydroxyanisole, myo-inositol, curcumin, esculetin,resveratrol and lycopene as inhibitors of benzo[a]pyrene plus 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis in A/J mice

The potential activities of butylated hydroxyanisole (BHA), myo-inositol, c urcumin, esculetin, resveratrol and lycopene-enriched tomato oleoresin (LTO ) as chemopreventive agents against lung tumor induction in A/J mice by the tobacco smoke carcinogens benzo[a]pyrene (BaP) and 4-(methyl-nitrosamino)- 1-(3-pyridyl)-1-butanone (NNK) were evaluated. Groups of 20 A/J mice were t reated weekly by gavage with a mixture of BaP and NNK (3 mu mol each) for 8 weeks, then sacrificed 26 weeks after the first carcinogen treatment. Mice treated with BHA (20 or 40 mu mol) by gavage 2 h before each dose of BaP a nd NNK had significantly reduced lung tumor multiplicity, Treatment with BH A (20 or 40 mu mol) by gavage weekly or with dietary BHA (2000 ppm), curcum in (2000 ppm) or resveratrol (500 ppm) from 1 week after carcinogen treatme nt until termination had no effect on lung tumor multiplicity. Treatment wi th dietary myo-inositol (30 000 ppm) or esculetin (2000 ppm) from 1 week af ter carcinogen treatment until termination significantly reduced lung tumor multiplicity, with the effect of myo-inositol being significantly greater than that of esculetin. Treatment with dietary LTO (167, 1667 or 8333 ppm) from I week before carcinogen treatment until termination had no effect on lung tumor multiplicity. The results of this study demonstrate that BHA is an effective inhibitor of BaP plus NNK-induced lung tumorigenesis in A/J mi ce when administered during the period of carcinogen treatment and that, am ong the compounds tested, myo-inositol is most effective after carcinogen t reatment. (C) 1999 Published by Elsevier Science Ltd. All rights reserved.