PMID- 11280748 OWN - NLM STAT- MEDLINE DCOM- 20010419 LR - 20131121 IS - 0008-5472 (Print) IS - 0008-5472 (Linking) VI - 61 IP - 5 DP - 2001 Mar 1 TI - Modulation of experimental colon tumorigenesis by types and amounts of dietary fatty acids. PG - 1927-33 AB - Epidemiological studies and laboratory animal model assays suggest that a high intake of dietary fat promotes colorectal cancer. Several in vivo and in vitro studies support the hypothesis that omega-6 fatty acids promote colon tumorigenesis, whereas omega-3 fatty acids lack promoting activity. Fat intake in the United States traditionally includes high amounts (30% of total caloric intake) of saturated fat rather than omega-6 fatty acids. Therefore, the present study was designed to compare the modulatory effects of a high-fat diet containing mixed lipids (HFML), a diet rich in saturated fatty acids (the average American diet), a diet with fish oil (HFFO) that is rich in omega-3 fatty acids, and a low-fat corn oil diet (LFCO) on the formation of chemically induced colonic aberrant crypt foci (ACF) and tumors, cyclooxygenase (COX)-2 activity, and apoptosis during experimental colon carcinogenesis. At 5 weeks of age, groups of male F344 rats were fed a 5% corn oil diet (LFCO). At 7 weeks of age, rats intended for carcinogen treatment received s.c. injections of azoxymethane at a dose level of 15 mg/kg of body weight once weekly for 2 weeks. Beginning 1 day after the carcinogen treatment, groups of rats were then maintained on experimental diets containing 20% HFML or 20% HFFO. Rats were killed at 8, 23, or 38 weeks after azoxymethane treatment. Colonic ACF and tumors were evaluated histopathologically, and apoptosis was evaluated by the terminal deoxynucleotidyl transferase-mediated nick end labeling method. Colonic mucosae and tumor samples harvested at week 38 were analyzed for COX-2 synthetic activity and expression. The rats fed the HFML diet showed significantly increased total colonic ACF (P < 0.001-0.0001) with a multiplicity of > or = 4 aberrant crypts/focus (P < 0.0001) compared with the effects of the HFFO or LFCO diets at week 8, 23, and 38. Interestingly, there was a 2- to 3-fold increase (> or = 4) in multicrypt foci in rats given the HFML diet as compared with such foci in rats fed the HFFO or LFCO diets. By week 23, the HFML diet had significantly increased the incidence of colonic tumors (30-60%) and their multiplicity (100-141%) when compared with the effects of the LFCO or HFFO diets. At week 38, the HFML diet had induced 100% colon tumor incidence and a 4-fold multiplicity of adenocarcinomas compared with the LFCO and HFFO diets. At weeks 23 and 38, a significantly lower percentage of apoptotic colonic epithelial cells were observed in the tumors of animals fed the HFML diet as compared with those fed the HFFO diet. The HFML diet caused significantly increased levels of COX-2 activity in colon tumors (P < 0.05-0.01), and these tumors had enhanced levels of COX-2 expression as compared with those in assays with LFCO or HFFO diets. These observations demonstrate for the first time that HFML diets containing high levels of saturated fatty acids (such as those in Western diets) promote colon carcinogenesis. Although the mechanisms involved in colon tumor promotion by a HFML diet are not fully known, our results indicate that the modulation of eicosanoid production via the influence on COX activity and the suppression of apoptosis may play a key role in HFML diet-induced colon tumorigenesis. FAU - Rao, C V AU - Rao CV AD - Division of Nutritional Carcinogenesis, American Health Foundation, Valhalla, New York 10595, USA. anshacvr@ix.netcom.com FAU - Hirose, Y AU - Hirose Y FAU - Indranie, C AU - Indranie C FAU - Reddy, B S AU - Reddy BS LA - eng GR - CA 17613/CA/NCI NIH HHS/United States GR - CA-37663/CA/NCI NIH HHS/United States GR - CA-80003/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Cancer Res JT - Cancer research JID - 2984705R RN - 0 (Carcinogens) RN - 0 (Dietary Fats) RN - 0 (Fatty Acids) RN - 0 (Fish Oils) RN - 0 (Isoenzymes) RN - 0 (Membrane Proteins) RN - 27YG812J1I (Arachidonic Acid) RN - 8001-30-7 (Corn Oil) RN - EC 1.14.99.1 (Cyclooxygenase 1) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - EC 1.14.99.1 (Prostaglandin-Endoperoxide Synthases) RN - EC 1.14.99.1 (Ptgs1 protein, rat) RN - MO0N1J0SEN (Azoxymethane) SB - IM MH - Animals MH - Apoptosis MH - Arachidonic Acid/metabolism MH - Azoxymethane MH - Body Weight/drug effects MH - Carcinogens MH - Colonic Neoplasms/chemically induced/*etiology/pathology MH - Corn Oil/administration & dosage MH - Cyclooxygenase 1 MH - Cyclooxygenase 2 MH - Dietary Fats/*administration & dosage MH - Fatty Acids/administration & dosage MH - Fish Oils/administration & dosage MH - Intestinal Mucosa/cytology/metabolism MH - Isoenzymes/metabolism MH - Male MH - Membrane Proteins MH - Precancerous Conditions/chemically induced/etiology/pathology MH - Prostaglandin-Endoperoxide Synthases/metabolism MH - Rats MH - Rats, Inbred F344 EDAT- 2001/03/31 10:00 MHDA- 2001/04/21 10:01 CRDT- 2001/03/31 10:00 PHST- 2001/03/31 10:00 [pubmed] PHST- 2001/04/21 10:01 [medline] PHST- 2001/03/31 10:00 [entrez] PST - ppublish SO - Cancer Res. 2001 Mar 1;61(5):1927-33.