Patchy field defects of apoptosis resistance and dedifferentiation in flat mucosa of colon resections from colon cancer patients

被引:30
作者
Bernstein, H
Holubec, H
Warneke, JA
Garewal, H
Earnest, DL
Payne, CM
Roe, DJ
Cui, HY
Jacobson, EL
Bernstein, C [1 ]
机构
[1] Univ Arizona, Coll Med, Dept Immunol & Microbiol, Tucson, AZ 85724 USA
[2] Univ Arizona, Dept Surg, Tucson, AZ 85724 USA
[3] Univ Arizona, Dept Med, Tucson, AZ 85724 USA
[4] Univ Arizona, Dept Pharmacol & Toxicol, Tucson, AZ 85724 USA
[5] Univ Arizona, Coll Publ Hlth, Tucson, AZ 85724 USA
[6] Univ Arizona, Arizona Canc Ctr, Tucson, AZ 85724 USA
[7] Tucson Vet Affairs Hosp, Tucson, AZ USA
[8] Univ Kentucky, Lucille P Markey Canc Ctr, Lexington, KY 40536 USA
关键词
field defects; apoptosis resistance; differentiation; colon cancer; Dolichos biflorus agglutinin;
D O I
10.1245/aso.2002.9.5.505
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Abnormal areas in normal-appearing flat colonic mucosa (field defects) may predispose individuals to colon cancer. Markers of field defects would indicate cancer risk. Methods: We evaluated apoptosis capability, dedifferentiation, frequency of simple aberrant crypts, aberrant crypt foci, microadenomas, and total nicotinamide adenine dinucleotide levels at locations within normal-appearing flat mucosa obtained from colon resections. Results: Among goblet cells from colonic mucosa samples of individuals without colonic neoplasia, there was a high mean deoxycholate-induced apoptotic index (AI) of 59.1% and high Dolichos biflorus agglutinin (DBA) lectin reactivity (differentiation) in 85.0% of samples. In contrast, flat mucosa samples from colon cancer patients had a significantly (P < .01) lower average AI of 37.4%, and a significantly (P = .03) lower percentage (40.5%) had high DBA reactivity. For colon cancer patients, AI and DBA reactivity values were patchy within a resection. Nicotinamide adenine dinucleotide levels were highly variable among individuals without neoplasia, and aberrant crypt foci and microadenomas were rare. Conclusions: At and aberrant DBA reactivity are promising indicators of colon cancer risk. Our results attest to the importance of obtaining multiple samples to assess colon cancer risk because of the patchy nature of field defects.
引用
收藏
页码:505 / 517
页数:13
相关论文
共 35 条
[11]   Effects of soy or rye supplementation of high-fat diets on colon tumour development in azoxymethane-treated rats [J].
Davies, MJ ;
Bowey, EA ;
Adlercreutz, H ;
Rowland, IR ;
Rumsby, PC .
CARCINOGENESIS, 1999, 20 (06) :927-931
[12]   A GENETIC MODEL FOR COLORECTAL TUMORIGENESIS [J].
FEARON, ER ;
VOGELSTEIN, B .
CELL, 1990, 61 (05) :759-767
[13]  
Garewal H, 1996, CANCER RES, V56, P1480
[14]   SODIUM-BUTYRATE INDUCES APOPTOSIS IN HUMAN COLONIC TUMOR-CELL LINES IN A P53-INDEPENDENT PATHWAY - IMPLICATIONS FOR THE POSSIBLE ROLE OF DIETARY FIBER IN THE PREVENTION OF LARGE-BOWEL CANCER [J].
HAGUE, A ;
MANNING, AM ;
HANLON, KA ;
HUSCHTSCHA, LI ;
HART, D ;
PARASKEVA, C .
INTERNATIONAL JOURNAL OF CANCER, 1993, 55 (03) :498-505
[15]  
HEERDT BG, 1994, CANCER RES, V54, P3288
[16]   Switch from monoallelic to biallelic human IGF2 promoter methylation during aging and carcinogenesis [J].
Issa, JPJ ;
Vertino, PM ;
Boehm, CD ;
Newsham, IF ;
Baylin, SB .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (21) :11757-11762
[17]  
Jackson AL, 1998, GENETICS, V148, P1483
[18]   NIACIN DEFICIENCY AND CANCER IN WOMEN [J].
JACOBSON, EL .
JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION, 1993, 12 (04) :412-416
[19]  
Jacobson EL, 1997, METHOD ENZYMOL, V280, P221
[20]   Mapping the role of NAD metabolism in prevention and treatment of carcinogenesis [J].
Jacobson, EL ;
Shieh, WM ;
Huang, AC .
MOLECULAR AND CELLULAR BIOCHEMISTRY, 1999, 193 (1-2) :69-74