Inhibition effect of Vitamine E δ-tocotrienol on PhIP/DSS-induced colon carcinogenesis in CYP1A-humanized mice (LB325)

Our previous research indicated that combination of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), the most abundant heterocyclic amine produced during the cooking of meats and fish, with dextran sodium sulfate (DSS) rapidly induced colon carcinogenesis in transgenic CYP1A-humanized mice (hCYP1A-mice). Herein, we modulated the dosage of DSS (0.8-1.5%) to establish a suitable model for cancer prevention research and to evaluate the inhibition effect of δ-tocotrienol (δ-T3) on colon carcinogenesis. The treatment with 200 mg/kg PhIP, followed by 1% DSS in the drinking water for 7 days moderately induced colon carcinogenesis in hCYP1A-mice with a tumor multiplicity of 4.17 ± 0.58 at week 8. Tumor multiplicity was reduced in 0.025% and 0.5% δ-T3 treatment groups by 49% (P < 0.05) and 58% (P < 0.01), respectively. Supplementation with δ-T3 also increased the respective levels of tocotrienol in the serum and colon tissues. These results demonstrate the inhibitory effect of δ-T3 against colon carcinogene...