Do aberrant crypt foci have predictive value for the occurrence of colorectal tumours? Potential of gene expression profiling in tumours.
The effects of different dietary compounds on the formation of aberrant crypt foci (ACF) and colorectal tumours and on the expression of a selection of genes were studied in rats. Azoxymethane-treated male F344 rats were fed either a control diet or a diet containing 10% wheat bran (WB), 0.2% curcumin (CUR), 4% rutin (RUT) or 0.04% benzyl isothiocyanate (BIT) for 8 months. ACF were counted after 7, 15 and 26 weeks. Tumours were scored after 26 weeks and 8 months. We found that the WB and CUR diets inhibited the development of colorectal tumours. In contrast, the RUT and BIT diets rather enhanced (although not statistically significantly) colorectal carcinogenesis. In addition, the various compounds caused different effects on the development of ACF. In most cases the number or size of ACF was not predictive for the ultimate tumour yield. The expression of some tumour-related genes was significantly different in tumours from the control group as compared to tumours from the treated groups. It was concluded that WB and CUR, as opposed to RUT and BIT, protects against colorectal cancer and that ACF are unsuitable as biomarker for colorectal cancer. Effects of the different dietary compounds on metalloproteinase 1 (TIMP-1) expression correlated well with the effects of the dietary compounds on the ultimate tumour yield.
TNO Nutrition and Food Research, Department of Toxicology and Applied Pharmacology, Utrechtseweg 48, P.O. Box 360, Zeist, AJ 3700, The Netherlands. wijnands@voeding.tno.nl
M V W
MV
Wijnands
M J
MJ
van Erk
R P
RP
Doornbos
C A M
CA
Krul
R A
RA
Woutersen
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D014408:Biomarkers, Tumor; D001835:Body Weight; D015179:Colorectal Neoplasms / Q000473:pathology*; D017931:DNA Primers; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D004032:Diet; D004435:Eating / Q000502:physiology; D004734:Energy Metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D007413:Intestinal Mucosa / Q000473:pathology*; D008297:Male; D011237:Predictive Value of Tests; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis / Q000235:genetics
D016588:Anticarcinogenic Agents; D014408:Biomarkers, Tumor; D017931:DNA Primers; D018076:DNA, Complementary; D012334:RNA, Neoplasm; D019715:Tissue Inhibitor of Metalloproteinase-1