Reduced colitis-associated colon cancer in Fat-1 (n-3 fatty acid desaturase) transgenic mice.
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, compared 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.
Jia
Qian
Q
Department of Nutrition and Food Science, Intercollegiate Faculty of Nutrition, Texas A&M University, Houston, USA.
Lupton
Joanne R
JR
Smith
Roger
R
Weeks
Brad R
BR
Callaway
Evelyn
E
Davidson
Laurie A
LA
Kim
Wooki
W
Fan
Yang-Yi
YY
Yang
Peiying
P
Newman
Robert A
RA
Kang
Jing X
JX
McMurray
David N
DN
Chapkin
Robert S
RS
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism; D017209:Apoptosis; D017252:CD3 Complex / Q000096:biosynthesis; D015704:CD4 Antigens / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D003092:Colitis / Q000235:genetics / Q000473:pathology*; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology*; D044943:Fatty Acid Desaturases / Q000235:genetics* / Q000502:physiology*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010743:Phospholipids / Q000378:metabolism
D000970:Antineoplastic Agents; D017252:CD3 Complex; D015704:CD4 Antigens; D005231:Fatty Acids, Unsaturated; D010743:Phospholipids; D044943:Fatty Acid Desaturases