title: Wheat bran decreases aberrant crypt foci, preserves normal proliferation, and increases intraluminal butyrate levels in experimental colon cancer.
abstract: BACKGROUND
  Dietary wheat bran protects against colon cancer, but the mechanism(s) of this effect is not known. Butyrate, produced by colonic bacterial fermentation of dietary polysaccharides, such as wheat bran, induces apoptosis and decreases proliferation in colon cancer cell lines. Whether similar effects occur in vivo is not well defined. We hypothesized that wheat bran's antineoplastic effects in vivo may be mediated in part by butyrate's modulation of apoptosis and proliferation.
  
  
  METHODS
  Male F344 rats were fed wheat bran-supplemented or an isocaloric, isonitrogenous fiber-free diet. Rats were treated with one dose of the carcinogen azoxymethane or vehicle with sacrifice after 5 days (tumor initiation); or two doses (days O and 7) with sacrifice after 56 days (tumor promotion). Study variables included fecal butyrate levels and the intermediate biomarkers of colon carcinogenesis, aberrant crypt foci (ACF), and changes in crypt cell proliferation and apoptosis.
  
  
  RESULTS
  During tumor initiation, wheat bran produced greater apoptosis (p = .01), a trend toward less proliferation, and preserved the normal zone of proliferation (p = .01). At tumor promotion, wheat bran decreased the number of ACF (proximal colon, p = .005; distal colon, p = .047) and maintained the normal proliferative zone. The fiber-free diet shifted the zone of proliferation into the premalignant pattern in both studies. Wheat bran produced significantly higher fecal butyrate (p = .01; .004, .00001) levels than the fiber-free diet throughout the tumor promotion study.
  
  
  CONCLUSIONS
  Wheat bran increased apoptosis and controlled proliferation during tumor initiation and resulted in decreased ACF. Wheat bran's antineoplastic effects occurred early after carcinogen exposure, and were associated with increased fecal butyrate levels.
authors.affiliation: Harrison Department of Surgical Research, Department of Surgery, University of Pennsylvania Medical Center, Philadelphia, USA.
authors.forename: C W
authors.initials: CW
authors.lastname: Compher
authors.forename: W L
authors.initials: WL
authors.lastname: Frankel
authors.forename: J
authors.initials: J
authors.lastname: Tazelaar
authors.forename: J A
authors.initials: JA
authors.lastname: Lawson
authors.forename: S
authors.initials: S
authors.lastname: McKinney
authors.forename: S
authors.initials: S
authors.lastname: Segall
authors.forename: B P
authors.initials: BP
authors.lastname: Kinosian
authors.forename: N N
authors.initials: NN
authors.lastname: Williams
authors.forename: J L
authors.initials: JL
authors.lastname: Rombeau
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis; D002087:Butyrates / Q000378:metabolism*; D002455:Cell Division; D003106:Colon / Q000473:pathology*; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control; D004043:Dietary Fiber / Q000494:pharmacology* / Q000627:therapeutic use; D005243:Feces / Q000737:chemistry; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D014908:Triticum
chemical_list: D016588:Anticarcinogenic Agents; D002087:Butyrates; D004043:Dietary Fiber