title: Advanced glycation end products (AGE) induce the receptor for AGE in the colonic mucosa of azoxymethane-injected Fischer 344 rats fed with a high-linoleic acid and high-glucose diet.
abstract: BACKGROUND
  Advanced glycation end products (AGE) and the receptor for advanced glycation end products (RAGE) are closely associated with colorectal cancer progression. The association between RAGE and AGE in colon carcinogenesis needs to be clarified.
  
  
  METHODS
  Levels of RAGE and AGE were examined in azoxymethane (AOM)-injected Fischer 344 rats fed a control diet (Group C), a 15 % linoleic acid (LA) diet (Group L), a control diet with 10 % glucose drink (Group G), and a 15 % LA diet with 10 % glucose drink (Group L + G). Group L + G showed the most pronounced increase of body weight, blood sugar, and serum insulin.
  
  
  RESULTS
  The rats in Group L + G showed the most pronounced multiplicity of aberrant crypt foci (ACF) and carcinomas with increased mucosal RAGE and AGE. IEC6 rat intestinal epithelial cells treated with AGE showed increased RAGE expression, which was inhibited by treatment with metformin or losartan. In the AOM-injected rat colon cancer model, the levels of RAGE and AGE, and the multiplicity of ACF and carcinomas, in Group L + G rats were suppressed by treatment with metformin or losartan.
  
  
  CONCLUSIONS
  These results suggest that AGE-RAGE induced by high-LA and high-glucose diets substantially enhances colon cancer development; thus, suppression of AGE-RAGE could be a potential target for colon cancer chemoprevention.
authors.affiliation: Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan.
authors.forename: Takasumi
authors.initials: T
authors.lastname: Shimomoto
authors.forename: Yi
authors.initials: Y
authors.lastname: Luo
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ohmori
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Chihara
authors.forename: Kiyomu
authors.initials: K
authors.lastname: Fujii
authors.forename: Tomonori
authors.initials: T
authors.lastname: Sasahira
authors.forename: Ayumi
authors.initials: A
authors.lastname: Denda
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kuniyasu
mesh_terms: D000818:Animals; D001397:Azoxymethane / Q000494:pharmacology; D001835:Body Weight; D002273:Carcinogens; D018929:Cell Culture Techniques; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism*; D004032:Diet; D004797:Enzyme-Linked Immunosorbent Assay; D005947:Glucose / Q000494:pharmacology*; D017127:Glycation End Products, Advanced / Q000187:drug effects / Q000378:metabolism*; D015151:Immunoblotting; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D019787:Linoleic Acid / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000187:drug effects / Q000378:metabolism*
chemical_list: D002273:Carcinogens; D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D019787:Linoleic Acid; D005947:Glucose; D001397:Azoxymethane