Carcinogenicity of deoxycholate, a secondary bile acid

被引:281
作者
Bernstein, Carol [1 ]
Holubec, Hana [1 ]
Bhattacharyya, Achyut K. [2 ,3 ]
Huy Nguyen [1 ]
Payne, Claire M. [1 ,2 ]
Zaitlin, Beryl [4 ]
Bernstein, Harris [1 ,2 ]
机构
[1] Univ Arizona, Coll Med, Dept Cell Biol & Anat, Tucson, AZ 85724 USA
[2] Univ Arizona, Arizona Canc Ctr, Tucson, AZ 85724 USA
[3] Univ Arizona, Coll Med, Dept Pathol, Tucson, AZ 85724 USA
[4] Univ Calgary, Dept Civil Engn, Calgary, AB T2N 1N4, Canada
关键词
Colon cancer; Deoxycholate; Adenocarcinoma; Chlorogenic acid; COLON EPITHELIAL-CELLS; NF-KAPPA-B; MULTIPLE STRESS-INDUCER; COLORECTAL-CANCER; OXIDATIVE STRESS; INDUCED APOPTOSIS; LARGE-BOWEL; DNA-DAMAGE; GENOMIC INSTABILITY; CHLOROGENIC ACID;
D O I
10.1007/s00204-011-0648-7
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
High dietary fat causes increased bile acid secretion into the gastrointestinal tract and is associated with colon cancer. Since the bile acid deoxycholic acid (DOC) is suggested to be important in colon cancer etiology, this study investigated whether DOC, at a high physiologic level, could be a colon carcinogen. Addition of 0.2% DOC for 8-10 months to the diet of 18 wild-type mice induced colonic tumors in 17 mice, including 10 with cancers. Addition of the antioxidant chlorogenic acid at 0.007% to the DOC-supplemented diet significantly reduced tumor formation. These results indicate that a high fat diet in humans, associated with increased risk of colon cancer, may have its carcinogenic potential mediated through the action of bile acids, and that some dietary anti-oxidants may ameliorate this carcinogenicity.
引用
收藏
页码:863 / 871
页数:9
相关论文
共 79 条
[1]   Phase III trial of ursodeoxycholic acid to prevent colorectal adenoma recurrence [J].
Alberts, DS ;
Martínez, ME ;
Hess, LM ;
Einspahr, JG ;
Green, SB ;
Bhattacharyya, AK ;
Guillen, J ;
Krutzsch, M ;
Batta, AK ;
Salen, G ;
Fales, L ;
Koonce, K ;
Parish, D ;
Clouser, M ;
Roe, D ;
Lance, P .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2005, 97 (11) :846-853
[2]   A "field change" of inhibited apoptosis occurs in colorectal mucosa adjacent to colorectal adenocarcinoma [J].
Badvie, S. ;
Hanna-Morris, A. ;
Andreyev, H. J. N. ;
Cohen, P. ;
Saini, S. ;
Allen-Mersh, T. G. .
JOURNAL OF CLINICAL PATHOLOGY, 2006, 59 (09) :942-946
[3]   UNCONJUGATED SECONDARY BILE-ACIDS IN THE SERUM OF PATIENTS WITH COLORECTAL ADENOMAS [J].
BAYERDORFFER, E ;
MANNES, GA ;
OCHSENKUHN, T ;
DIRSCHEDL, P ;
WIEBECKE, B ;
PAUMGARTNER, G .
GUT, 1995, 36 (02) :268-273
[4]  
Bernstein C, 1999, CANCER RES, V59, P2353
[5]   Bile acids as carcinogens in human gastrointestinal cancers [J].
Bernstein, H ;
Bernstein, C ;
Payne, CM ;
Dvorakova, K ;
Garewal, H .
MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH, 2005, 589 (01) :47-65
[6]   A proteomic study of resistance to deoxycholate-induced apoptosis [J].
Bernstein, H ;
Payne, CM ;
Kunke, K ;
Crowley-Weber, CL ;
Waltmire, CN ;
Dvorakova, K ;
Holubec, H ;
Bernstein, C ;
Vaillancourt, RR ;
Raynes, DA ;
Guerriero, V ;
Garewal, H .
CARCINOGENESIS, 2004, 25 (05) :681-692
[7]   Patchy field defects of apoptosis resistance and dedifferentiation in flat mucosa of colon resections from colon cancer patients [J].
Bernstein, H ;
Holubec, H ;
Warneke, JA ;
Garewal, H ;
Earnest, DL ;
Payne, CM ;
Roe, DJ ;
Cui, HY ;
Jacobson, EL ;
Bernstein, C .
ANNALS OF SURGICAL ONCOLOGY, 2002, 9 (05) :505-517
[8]   Deoxycholate-induced colitis is markedly attenuated in Nos2 knockout mice in association with modulation of gene expression profiles [J].
Bernstein, Harris ;
Holubec, Hana ;
Bernstein, Carol ;
Ignatenko, Natalia A. ;
Gerner, Eugene ;
Dvorak, Katerina ;
Besselsen, David ;
Blohm-Mangone, Karen Ann ;
Padilla-Torres, Jose ;
Dvorakova, Barbora ;
Garewal, Harinder ;
Payne, Claire M. .
DIGESTIVE DISEASES AND SCIENCES, 2007, 52 (03) :628-642
[9]   Bile acids as endogenous etiologic agents in gastrointestinal cancer [J].
Bernstein, Harris ;
Bernstein, Carol ;
Payne, Claire M. ;
Dvorak, Katerina .
WORLD JOURNAL OF GASTROENTEROLOGY, 2009, 15 (27) :3329-3340
[10]   Secondary bile acid induced DNA damage in HT29 cells: Are free radicals involved? [J].
Booth, LA ;
Gilmore, IT ;
Bilton, RF .
FREE RADICAL RESEARCH, 1997, 26 (02) :135-144