title: A chemoprotective fish oil- and pectin-containing diet temporally alters gene expression profiles in exfoliated rat colonocytes throughout oncogenesis.
abstract: We have demonstrated that fish oil- and pectin-containing (FO/P) diets protect against colon cancer compared with corn oil and cellulose (CO/C) by upregulating apoptosis and suppressing proliferation. To elucidate the mechanisms whereby FO/P diets induce apoptosis and suppress proliferation during the tumorigenic process, we analyzed the temporal gene expression profiles from exfoliated rat colonocytes. Rats consumed diets containing FO/P or CO/C and were injected with azoxymethane (AOM; 2 times, 15 mg/kg body weight, subcutaneously). Feces collected at initiation (24 h after AOM injection) and at aberrant crypt foci (ACF) (7 wk postinjection) and tumor (28 wk postinjection) stages of colon cancer were used for poly (A)+ RNA extraction. Gene expression signatures were determined using Codelink arrays. Changes in phenotypes (ACF, apoptosis, proliferation, and tumor incidence) were measured to establish the regulatory controls contributing to the chemoprotective effects of FO/P. At initiation, FO/P downregulated the expression of 3 genes involved with cell adhesion and enhanced apoptosis compared with CO/C. At the ACF stage, the expression of genes involved in cell cycle regulation was modulated by FO/P and the zone of proliferation was reduced in FO/P rats compared with CO/C rats. FO/P also increased apoptosis and the expression of genes that promote apoptosis at the tumor endpoint compared with CO/C. We conclude that the effects of chemotherapeutic diets on epithelial cell gene expression can be monitored noninvasively throughout the tumorigenic process and that a FO/P diet is chemoprotective in part due to its ability to affect expression of genes involved in apoptosis and cell cycle regulation throughout all stages of tumorigenesis.
authors.affiliation: Faculty of Nutrition Texas A&M University, College Station, TX 77843, USA.
authors.forename: Youngmi
authors.initials: Y
authors.lastname: Cho
authors.forename: Hyemee
authors.initials: H
authors.lastname: Kim
authors.forename: Nancy D
authors.initials: ND
authors.lastname: Turner
authors.forename: John C
authors.initials: JC
authors.lastname: Mann
authors.forename: Jiawei
authors.initials: J
authors.lastname: Wei
authors.forename: Stella S
authors.initials: SS
authors.lastname: Taddeo
authors.forename: Laurie A
authors.initials: LA
authors.lastname: Davidson
authors.forename: Naisyin
authors.initials: N
authors.lastname: Wang
authors.forename: Marina
authors.initials: M
authors.lastname: Vannucci
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Carroll
authors.forename: Robert S
authors.initials: RS
authors.lastname: Chapkin
authors.forename: Joanne R
authors.initials: JR
authors.lastname: Lupton
mesh_terms: D000818:Animals; D001397:Azoxymethane / Q000633:toxicity; D002453:Cell Cycle / Q000235:genetics; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control*; D004032:Diet; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage; D019422:Dietary Sucrose / Q000008:administration & dosage; D020895:Enterocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005243:Feces / Q000737:chemistry / Q000166:cytology; D005395:Fish Oils / Q000008:administration & dosage*; D020869:Gene Expression Profiling; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010368:Pectins / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004042:Dietary Fats, Unsaturated; D019422:Dietary Sucrose; D005395:Fish Oils; D012333:RNA, Messenger; D010368:Pectins; D001397:Azoxymethane