Gamma Tocopherol Reduces Aberrant Crypt Foci in Azoxymethane-Treated Fisher 344 Rats
T Giorgadze, G Axelson, S Whaley, M Brannon, W Stone, S Campbell. Wayne State University, Detroit, MI; East Tennessee State University, Johnson City, TN
Background: Aberrant crypt foci (ACF) are early neoplastic (dysplastic) lesions that are important in understanding colonic carcinogenesis in carcinogen-treated animals. Recent studies have shown that y-Tocopherol (the most common of four Vitamin E isoforms in the typical American diet) may play unique role in preventing colon cancer. We examined effects of dietary γ-Tocopherol (γT) on development of colonic ACF in azoxymethane-treated (AOM) Fisher 344 Rats.
Design: The rats were treated with 2 doses of AOM (15 mg/kg weight) by intraperitoneal injection on weeks 2 and 3 following weaning (age 6 weeks). Three AOM-treated groups were studied (12 rats in each). Group 1 (G1) were fed with no γT addition to the diet, groups 2 (G2) and 3 (G3) were fed γT at 0.4 mg/day (30 IU, low dose) and 5.75 mg/day (400 IU, high dose), respectively, in a modified AIN-76A diet (no vitamin E added, corn oil stripped to remove exogenous vitamin E). Control rats with no AOM treatment were fed 0.4 mg/day γT. Animals were sacrificed at 16 weeks of age. Colons were cut open and stained fresh with methylene blue (0.2% in buffered saline) for 60 min. The mucosal surface was equally divided into proximal and distal segments. The number (#) of ACF and crypt multiplicity (<4 or >4 crypts per focus) were counted at 100x magnification in each colonic segment.
Results: There was no difference in growth rate (rat mass) between the groups. G1 (γT-deficient) and G3 (high dose γT fed) rats developed significantly higher number of ACF compared to low dose γT fed G2 rats (p<0.001). Table 1 shows number of ACF and multiplicity (AVG and STD) in each group.
|Groups||Total # of ACF||<4 crypts||>4 crypts|
|G1 (no γT )||33+/-5.2||18.9+/-3.4||15.8+/-6.22|
|G2 (30 IU γT )||18.9+/-4.1||10.5+/-8.3||8.3+/-4.1|
|G3 (400 IU γT)||46.1+/-8.6||26.1+/-9.8||20.7+/-7.8|