TY - JOUR
T1 - Reduced colitis-associated colon cancer in fat-1 (n-3 fatty acid desaturase) transgenic mice
AU - Jia, Qian
AU - Lupton, Joanne R.
AU - Smith, Roger
AU - Weeks, Brad R.
AU - Callaway, Evelyn
AU - Davidson, Laurie A.
AU - Kim, Wooki
AU - Fan, Yang Yi
AU - Yang, Peiying
AU - Newman, Robert A.
AU - Kang, Jing X.
AU - McMurray, David N.
AU - Chapkin, Robert S.
PY - 2008/5/15
Y1 - 2008/5/15
N2 - Bioactive food components containing n-3 polyunsaturated fatty acids (PUFA) modulate multiple determinants that link inflammation to cancer initiation and progression. Therefore, in this study, fat-1 transgenic mice,which convert endogenous n-6 PUFA to n-3 PUFA in multiple tissues,were injected with azoxymethane followed by three cycles of dextran sodium sulfate (DSS) to induce colitis-associated cancer. Fat-1 mice exhibited a reduced number of colonic adenocarcinomas per mouse (1.05 ± 0.29 versus 2.12 ± 0.51, P = 0.033), elevated apoptosis (P = 0.03), and a decrease in n-6 PUFA-derived eicosanoids, compare d with wild-type (wt) mice. To determine whether the chemoprotective effects of n-3 PUFA could be attributed to its pleiotropic anti-inflammatory properties, colonic inflammation and injury scores were evaluated 5 days after DSS exposure followed by either a 3-day or 2-week recovery period. There was no effect of n-3 PUFA at 3 days. However,following a 2-week recovery period, colonic inflammation and ulceration scores returned to pretreatment levels compared with 3-day recovery only in fat-1 mice. For the purpose of examining the specific reactivity of lymphoid elements in the intestine,CD3+ T cells,CD4+ T helper cells, and macrophages from colonic lamina propria were quantified. Comparison of 3-day versus 2-week recovery time points revealed that fat-1 mice exhibited decreased (P < 0.05) CD3+, CD4+ T helper, and macrophage cell numbers per colon as compared with wt mice. These results suggest that the antitumorigenic effect of n-3 PUFA may be mediated,in part, via its anti-inflammatory properties.
AB - Bioactive food components containing n-3 polyunsaturated fatty acids (PUFA) modulate multiple determinants that link inflammation to cancer initiation and progression. Therefore, in this study, fat-1 transgenic mice,which convert endogenous n-6 PUFA to n-3 PUFA in multiple tissues,were injected with azoxymethane followed by three cycles of dextran sodium sulfate (DSS) to induce colitis-associated cancer. Fat-1 mice exhibited a reduced number of colonic adenocarcinomas per mouse (1.05 ± 0.29 versus 2.12 ± 0.51, P = 0.033), elevated apoptosis (P = 0.03), and a decrease in n-6 PUFA-derived eicosanoids, compare d with wild-type (wt) mice. To determine whether the chemoprotective effects of n-3 PUFA could be attributed to its pleiotropic anti-inflammatory properties, colonic inflammation and injury scores were evaluated 5 days after DSS exposure followed by either a 3-day or 2-week recovery period. There was no effect of n-3 PUFA at 3 days. However,following a 2-week recovery period, colonic inflammation and ulceration scores returned to pretreatment levels compared with 3-day recovery only in fat-1 mice. For the purpose of examining the specific reactivity of lymphoid elements in the intestine,CD3+ T cells,CD4+ T helper cells, and macrophages from colonic lamina propria were quantified. Comparison of 3-day versus 2-week recovery time points revealed that fat-1 mice exhibited decreased (P < 0.05) CD3+, CD4+ T helper, and macrophage cell numbers per colon as compared with wt mice. These results suggest that the antitumorigenic effect of n-3 PUFA may be mediated,in part, via its anti-inflammatory properties.
UR - http://www.scopus.com/inward/record.url?scp=45549085184&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=45549085184&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-07-6251
DO - 10.1158/0008-5472.CAN-07-6251
M3 - Article
C2 - 18483285
AN - SCOPUS:45549085184
SN - 0008-5472
VL - 68
SP - 3985
EP - 3991
JO - Cancer Research
JF - Cancer Research
IS - 10
ER -