Dietary fish oil reduces DNA adduct formation while estradiol upregulates apoptosis in response to DNA damage in the rat colon.

ABSTRACT

BACKGROUND: Dietary fish oil is associated with a decrease in colon cancer incidence in part through a reduction in DNA adduct formation and an induction of colonocyte apoptosis. Estradiol (E(2)) has also been demonstrated to be protective against colon cancer incidence. Studies evaluating fish oil diets and DNA adduct formation in the colon have been conducted in male models without regard to possible interactions with E(2). AIMS: The aim of this study was to evaluate the effects of E(2) and fish oil both together and separately in female rats at the point of DNA damage. METHODS: Ovariectomized female Sprague-Dawley rats were fed either a corn oil or fish oil diet in the presence or absence of E(2) for two weeks prior to being sacrificed at four time points following injection with azoxymethane. O(6)-methyldeoxyguanosine (O(6)-MedG) DNA adducts and apoptosis were examined using immunohistochemistry. RESULTS: Dietary fish oil reduced DNA adduct formation independent of the presence of E(2) at both 9 and 12 h post carcinogen. E(2) itself did not suppress adduct formation. E(2) significantly induced apoptosis 12 h after carcinogen independent of diet, primarily in the luminal third of the crypts. Fish oil was not associated with increased colonocyte apoptosis. CONCLUSIONS: These data demonstrate that fish oil is protective against DNA damage in the colon regardless of gender through reduction of O(6)-MedG adduct formation. Additionally, E(2) is capable of inducing apoptosis directly at the point of DNA damage.