Poster Sessions

CANCER-19

Petra Tsuji

P. Tsuji, A. Sengupta, M.-H. Yoo, B. Carlson, C. Hitz, D. Hatfield, V. Gladyshev, C. Davis

Sep15 Ablation Reduces Carcinogen-induced Aberrant Crypt Formation In Vivo in Mouse Colon

Selenium, an essential micronutrient in the diet of mammals, is a cancer preventive agent and its protective effect is partially mediated through selenoproteins. Selenoprotein 15 (Sep15) has been associated recently with colorectal cancer. We conducted in vivo studies in Sep15 knockout mice measuring aberrant crypt foci (ACF) as putative preneoplastic lesions and thus as a surrogate biomarker for colon tumorigenesis. Additionally, because the availability of dietary selenium has been shown to regulate the expression of selenoproteins, the number of ACF in mice maintained on 0, 0.1 and 2.0 ug selenium/g diet were determined. Mice were given four weekly subcutaneous injections of the known colon carcinogen azoxymethane at 10 mg/kg body weight. Eight weeks after the last carcinogen dose, the large intestines were excised, fixed in ethanol and stained with methylene blue, and ACF were scored. Sep15 knockout mice showed significantly fewer ACF than controls (p<0.001). Additional dietary selenium did not significantly affect formation of ACF in Sep15 knockout mice. Livers were analyzed to determine mRNA and protein levels, and activities of selected selenoproteins were assayed. Based on these preliminary results, ablation of Sep15 in mice appears to result in a lower carcinogen-induced ACF formation in colon.