Chemoprevention of colorectal cancer: a systematic review in rats.
Clik here to go back to main page
Studies of colonic tumors & cancers in rats,
not yet linked to Medline (e.g., abstracts from congress)
- Bull A, Bird RP, Bruce WR, Nigro N, and Medline
A: Effect of calcium on azoxymethane induced intestinal tumors in rats.
Gastroenterology, 92, abstract #1332 (abstr), 1987.
EFFECT OF CALCIUM ON AZOXYMETHANE INDUCED INTESTINAL TUMORS IN RATS.
A.Bull, R.P.Bird, W.R.Bruce, N.Nigro, A.Medline,
Ludwig Inst. for Cancer Res., Toronto Branch, Toronto, Canada and
Wayne State Univ.Sch. of Medicine, Detroit, MI.
Two experimental protocols were used to evaluate the effect of dietary calcium on colon tumorigenesis. In the first (Study A) 120 male Sprague-Dawley rats weighing 100-125 g were divided into 4 dietary groups of 30 rats each. The diets were as follows: Calcium (Ca HP04) 0.1% or 1.0% of the diet was added to either a low fat (2% beef fat + 1% corn oil) diet or a high fat (29% beef fat + 1% corn oil) diet. The Ca:P was 1:1 in all diets. 25 rats in each group were given weekly sc injections of azoxymethane 8 mg/kg for 8 weeks. The other five rats in each group served as non carcinogen controls. Rats were killed and intestinal tumors tabulated 26 weeks after the first carcinogen injection.
In the second study (Study B) 160 F344 female rats received weekly injections of azoxymethane (sc 15 mg/kg for 2 weeks). One week later they were randomized into the 4 dietary groups mentioned above. Each group contained 40 treated and 10 control animals. Nine months after the first injection with carcinogen treatment animals were killed and examined for tumor incidence. Results for the large bowel tumors (average no of tumors/rat) are shown in the table:
-------------- 3% Fat ------------------ ------ 30% Fat ----------
-------- 0.1% Ca -- 1.0% Ca ---- ---- 0.1% Ca -- 1.0% Ca
Study A : 2.9 ------ 3.5 ----------- ------- 3.3 --------- 5.7
Study B : 1.4 ------ 1.7 ----------- ------- 2.0 --------- 2.7
Total tumor yield irrespective of the size and type was enhanced by both high levels of calcium and high levels of fat in the diet. Consequently, the results of this animal experiment do not support the hypothesis that supplemental calcium inhibits intestinal tumor formation.
Flynn C., Masako Nakanishi, David Montrose, Michael Johnson, Daniel W. Rosenberg.
Promotional effect of deoxycholic acid in murine model resistant to colorectal cancer
Proc Amer Assoc Cancer Res 2005;46:[Abstract #1198].
AKR/J mice are resistant to the tumorigenic properties of the colon carcinogen, azoxymethane (AOM). Upon AOM exposure, only limited numbers of preneoplastic lesions, referred to as aberrant crypt foci (ACF), are formed in the colon, and tumor progression is a rare event. To determine whether inherent tumor resistance can be overcome by concomitant exposure to a dietary tumor promoter, AOM-exposed AKR/J mice were fed a diet containing 0.25% deoxycholic acid (DCA). DCA exposure was begun one week prior to or one week after initiation with AOM. Mice started on the DCA diet prior to AOM developed a higher number of ACF (2-fold) compared to AOM exposed non-DCA fed mice (15.5 ± 0.96 vs. 6.17 ± 0.48 respectively). However, when DCA exposure was started after AOM treatment (post-initiation), ACF formation was further enhanced (up to 4-fold) and colonic lesions were characterized by a higher degree of dysplasia (34.00 ± 1.22). The increase in ACF number was correlated with the presence of nuclear b-catenin, assessed by immunohistochemical staining. In fact, 77% of ACF in the colons of mice fed DCA after AOM had positive b-catenin nuclear staining. In contrast, only 33% of ACF from mice exposed to DCA prior to AOM treatment contained positive staining nuclei. These results indicate that exposure to DCA, an important digestive component, is sufficient to sensitize a resistant colonic epithelium to formation of high-grade dysplasia, and further suggest that b-catenin nuclear translocation may play a key role in DCA-mediated colonic dysplasia.
- Madar Z, Weiss O, Timar B, Gurevich P, and
Zusman I: The effects of high-fiber diets on chemically induced colon cancer in
rats. The Cancer Journal, 9, 207-211, 1996.
Martinez-Ferrer, Magaly, Martha Verghese, Lloyd Walker, Louis Shackelford.
Lycopene reduces incidence of azoxymethane induced colon tumors in Fisher 344 male rats during initiation and progression stages.
Proc AACR, 45, AACR 95th annual meeting, Orlando, March 2004. 1524
Vanderbilt University - School of Medicine, Nashville, TN and Alabama A&M University, Normal, AL.
Colorectal cancer is the third leading cause of cancer deaths in the United States. Several epidemiological studies have shown an inverse correlation between dietary intake of lycopene and the incidence of colon cancer. The objectives of this study were: (1) to determine the effect of dietary lycopene (400 ppm 7% fat and 400 ppm 14% fat) on chemically-induced colon tumorigenesis (end point tumor induction) in rats at tumor initiation and promotion stages, and (2) to determine the effect of dietary lycopene on the histopathology of tumors. Fisher 344 male weanling rats were divided into 8 groups of rats and were assigned to: AIN 93G +7% fat and AIN 93G +14% fat (controls), AIN 93G +7% fat+400ppm lycopene and AIN 93G +14% fat + 400ppm lycopene diets. Each lycopene diet was fed during initiation (I), promotion (P) and initiation plus promotion (I+P) stages of carcinogenesis. All the rats except saline controls received 16 mg/kg body weight of AOM at 7 and 8 wk of age. The rats were sacrificed at 46 wk of age. Tumor incidence (%) in colon of rats in the AIN 93G+7% fat and AIN 93G+14% fat were 87 and 100. Tumor incidence (%) in colon of rats in the AIN 93G+7% fat + 400ppm lycopene and AIN 93G+14% fat + 400 ppm lycopene (I, P, I+P) was 76, 60, 45, 86, 55, and 35, respectively. Colon tumors per tumor bearing rats (TBR) were 1.9, 4.4, 1.4, 1.7, 1, 1.8, 2.1, and 1.1 for the AIN 93G (7% and 14% fat), lycopene 400 ppm 7% and lycopene 400 ppm 14% (I, P, I+P), respectively. Histopathology of colon tumors was also compared among groups. Rats fed higher fat showed a higher incidence of developing adenocarcinomas. Dietary lycopene showed an effect in reducing total number of tumors as well as tumor size. This study provides evidence that dietary lycopene suppresses AOM induced colon tumorigenesis in Fisher 344 male rats, especially at the (P) and (I+P) stage, and therefore, colon tumorigenesis may be highly sensitive to dietary intervention
Clik here to go back to main page & database
Denis E. Corpet & Sylviane Taché, 2002, Nutrition & Cancer - & - Denis E. Corpet & Fabrice Pierre, 2003, Cancer Epidemiol. Biomarkers Prevention
colorectal cancer chemoprevention database & Mirror site