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* Department of Nutrition and Food Science,
Center for Environmental and Rural Health, and
Department of Statistics, Texas A&M University, College Station, Texas 77843
To whom requests for reprints should be addressed at 1 213 Kleberg Building, 2253 TAMU, College Station, TX 778432253. E-mail: jlupton{at}tamu.edu
Although large intestine (LI) cancer is the second-leading cause of cancer-related deaths in the United States, small intestine (SI) cancer is relatively rare. Because oxidative DNA damage is one possible initiator of tumorigenesis, we investigated if the SI is protected against cancer because of a more appropriate response to oxidative DNA damage compared with the LI. Sixty rats were allocated to three treatment groups: 3% dextran sodium sulfate (DSS, a DNA-oxidizing agent) for 48 hrs, withdrawal (DSS for 48 hrs + DSS withdrawal for 48 hrs), or control (no DSS). The SI, compared with the LI, showed greater oxidative DNA damage (P < 0.001) as determined using a quantitative immunohistochemical analysis of 8-oxodeoxyguanosine (8-oxodG). The response to the DNA adducts in the SI was greater than in the LI. The increase of TdTmediated dUTP-biotin nick end labeling (TUNEL)-positive apoptosis after DSS treatment was greater in the SI compared with the LI (P < 0.001), and there was a positive correlation (P = 0.031) between DNA damage and apoptosis in the SI. Morphologically, DSS caused an extensive loss of crypt structure shown in lower crypt height (P = 0.006) and the number of intact crypts (P = 0.0001) in the LI, but not in the SI. These data suggest that the SI may be more protected against cancer by having a more dynamic response to oxidative damage that maintains crypt morphology, whereas the response of the LI makes it more susceptible to loss of crypt architecture. These differential responses to oxidative DNA damage may contribute to the difference in cancer susceptibility between these two anatomic sites of the intestine.
Key Words: small intestine colon oxidative DNA damage apoptosis cell proliferation
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