Abstract A42: The dietary agents indole-3-carbinol and myo-inositol prevent lung cancer induced by vinyl carbamate in A/J mice
Authors: Kassie Fekadu , Matise Ilze , Kalscheuer Stephen , Upadhyaya Pramod , Hecht Stephen 
Published: May 2012

Abstract
A42
Because of their expected safety, food-derived products could be highly interesting for development as chemopreventive agents. Among promising cancer preventive dietary agents are indole-3-carbinol (I3C) and myo-inositol (MI). I3C is derived from the enzymatic hydrolysis of indolyl glucosinolates contained in cruciferous vegetables. MI is found in a variety of animal and plant foods in its free form, as an inositol-containing phospholipid, and inositol hexaphosphate (IP6, phytic acid,). In earlier studies, we found that both I3C and MI prevent lung adenoma induced by tobacco smoke carcinogens in A/J mice. In the present study, we examined the efficacy of I3C and MI to prevent lung adenocarcinoma. Female A/J mice were injected i.p. with two doses of vinyl carbamate (VC, 0.32 mg per mouse) dissolved in physiological saline, 1 week apart, and then randomized into the different treatment groups. After waiting 1 week following the second injection of the carcinogen, mice were maintained either on untreated control diet, or diets supplemented with I3C (70 µmol/g diet) or MI (56 µmol/g diet) for 15 weeks. At necropsy, lungs were removed and grossly visible lesions on the surface of all lobes of the lung were counted and the size of the tumors determined using a dissecting microscope. Then, the left lobe of the lung from each mouse was preserved in buffered formalin for histopathological analysis. Mice treated with VC and fed conventional diet had 42.6 ± 11.9 lung tumors/mouse. Compared to mice treated with VC alone, carcinogen-treated mice given I3C or MI-supplemented diet had a significantly lower tumor multiplicity, 31.6 ±4.8 and 33.9 ± 6.1 lung tumors, corresponding to a reduction by 26% and 20% respectively (p = 0.0003 for VC + I3C group and p = 0.0005 for VC + MI group compared using Wilcoxon non-paramteric test). Classification of the tumors into three different size groups (&lt;1 mm, 1-2 mm, and &gt; 2 mm) showed that the multiplicity of only the larger tumors was reduced by the chemopreventive agents (25.4 ± 6.8, 16.4 ± 8.3 and 0.69 ±1.3 tumors/mouse for &lt; 1mm, 1-2 mm, and &gt; 2 mm size groups, respectively, in mice treated with VC alone versus 28.8 ± 4.9, 2.8 ± 2.0, and 0.05 ± 0.22 tumors/mouse in the group treated with VC + I3Cand26.8 ± 5.1, 6.7 ± 2.3, and 0.40 ± 0.6 tumors/mouse in VC + MI-treated mice). Furthermore, we determined the effect of the chemopreventive agents on the incidence and multiplicity of the different microscopic lesions (hyperplasia, adenoma, adenoma with cellular pleomorphism and adenocarcinoma). Preliminary results showed that I3C reduced the incidence (71% in the VC group versus 36% in the VC + I3C group) and multiplicity (1.1 /mouse in the VC group versus 0.4 /mouse in the VC + I3C group) of adenocarcinoma. I3C also reduced the multiplicity (3.6/mouse in the VC group versus 2.4 /mouse in the VC + I3C group) of adenoma with cellular pleomorphism lesions. In mice maintained on MI-supplemented diet, there was no change either in the incidence or multiplicity of adenocarcinoma but the multiplicity of adenoma with cellular pleomorphism lesions was markedly reduced (3.6/mouse in the VC group versus 1.5/mouse in the VC + MI group). The chemopreventive agents did not affect the incidence or multiplicity of hyperplastic or adenoma lesions. In conclusion, our results indicate the potential lung cancer chemopreventive effects of I3C and MI in former smokers.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A42.