Dietary fish oil reduces oxidative DNA damage in rat colonocytes.
Prolonged generation of reactive oxygen species by inflammatory mediators can induce oxidative DNA damage (8-oxodG formation), potentially resulting in intestinal tumorigenesis. Fish oil (FO), compared to corn oil (CO), has been shown to downregulate inflammation and upregulate apoptosis targeted at damaged cells. We hypothesized FO could protect the intestine against 8-oxodG formation during dextran sodium sulfate- (DSS-) induced inflammation. We provided 60 rats with FO- or CO-supplemented diets for 2 weeks with or without 3% DSS in drinking water for 48 h. Half the treated rats received 48 additional h of untreated water before termination. Due to DSS treatment, the intestinal epithelium had higher levels of 8-oxodG (p =.04), induction of repair enzyme OGG1 mRNA (p =.02), and higher levels of apoptosis at the top of colonic crypts (p =.01) and in surface cells (p <.0001). FO-fed rats, compared to CO, had lower levels of 8-oxodG (p =.05) and increased apoptosis (p =.04) in the upper crypt region; however, FO had no significant effect on OGG1 mRNA. We conclude that FO protects intestinal cells against oxidative DNA damage in part via deletion mechanisms.
Bancroft
Laura K
LK
Molecular and Cell Biology Group, Faculty of Nutrition, Texas A&M University, College Station, TX 77843-2471, USA.
Lupton
Joanne R
JR
Davidson
Laurie A
LA
Taddeo
Stella S
SS
Murphy
Mary E
ME
Carroll
Raymond J
RJ
Chapkin
Robert S
RS
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D003106:Colon / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D018736:DNA Adducts / Q000032:analysis / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects*; D045647:DNA Glycosylases / Q000235:genetics; D004032:Diet; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage / Q000494:pharmacology*; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005395:Fish Oils / Q000008:administration & dosage / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015430:Weight Gain / Q000187:drug effects
D016588:Anticarcinogenic Agents; D018736:DNA Adducts; D004042:Dietary Fats, Unsaturated; D005395:Fish Oils; D045647:DNA Glycosylases; C483741:OGG1 protein, rat