[1720] 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.

Table 1
GroupsTotal # of ACF<4 crypts>4 crypts
G1 (no γT )33+/-5.218.9+/-3.415.8+/-6.22
G2 (30 IU γT )18.9+/-4.110.5+/-8.38.3+/-4.1
G3 (400 IU γT)46.1+/-8.626.1+/-9.820.7+/-7.8
Control2+/-2.62+/-2.60


Interestingly, in all groups the average number of ACF was significantly higher in the distal (D) colon compared to the proximal (P). Average ACF ratio (D/P) were: 26.1/2.7 in G1; 23.0/4.1 in G2; 39.8/5.0 in G3. Between the groups, there was no significant difference in average number of the proximal colon ACF.
Conclusions: 1) There is dose-dependant response between the number of ACF and γT dosage. 2) Low dose γT addition to the daily diet has chemoprotective effect in colon carcinogenesis. 3) High dose dietary γT may be even more harmful than γT-deficiency.
Category: Pathobiology

Wednesday, March 24, 2010 9:30 AM

Poster Session V # 218, Wednesday Morning

 

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