[Omega-6 polyunsaturated fatty acid promotes colon carcinogenesis].
OBJECTIVE
To investigate whether ω-6 polyunsaturated fatty acid promotes colon carcinogenesis through downregulation of P53-dependent growth inhibition.


METHODS
Colon carcinogenesis was induced by injection of azoxymethane (AOM) intraperitoneally. Experimental animals were randomly divided into four groups, receiving regular diet and intraperitoneal injection of normal saline(control group), high ω-6 polyunsaturated fatty acid diet with intraperitoneal injection of normal saline(Corn oil group), regular diet with intraperitoneal injection of AOM(AOM group), or high ω-6 polyunsaturated fatty acid diet with intraperitoneal injection of AOM (Corn oil+AOM group). Aberrant crypt focis (ACFs) were observed after methylene blue staining and enumerated. Colonic mucosa PCNA and P53 expressions were assessed by RT-PCR and Western blotting, and location of P53 in the colon crypt focis was determined by immunohistochemical staining.


RESULTS
Amounts of ACFs was 1.2±0.3 in the control group, 1.3±0.4 in the Corn oil group, 41.0±4.8 in the AOM group, and 73.3±9.9 in the Corn oil+AOM group, the differences were statistically significant(P<0.05). The expression of P53 in normal crypt focis was higher than that in ACFs. High ω-6 polyunsaturated fatty acid dietary significantly promoted AOM-induced colon PCNA expression, and enhanced AOM-mediated P53 inhibition in colon mucosa.


CONCLUSIONS
High ω-6 polyunsaturated fatty acid diet can enhance AOM-induced inhibition of P53 in colon mucosa, resulting in overexpression of PCNA, formation of ACF, and carcinogenesis in the colon.
Department of Gastroenterology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China.
Xiao-liang
XL
Chen
Jian-zhong
JZ
Li
Li-xian
LX
Zeng
Ya-shi
YS
Zhan
Ying-hui
YH
Yang
Qi
Q
Yang
Hui-ling
HL
Liu
Bin
B
Wu
D000818:Animals; D003106:Colon / Q000187:drug effects* / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000009:adverse effects*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D005231:Fatty Acids, Unsaturated; D018809:Proliferating Cell Nuclear Antigen; D016159:Tumor Suppressor Protein p53