Impaired antioxidant defense system of colonic tissue and cancer development in dextran sulfate sodium-induced colitis in mice.
BACKGROUND
The mechanisms underlying the frequent development of carcinomas associated with ulcerative colitis (UC) are not understood. Cellular antioxidants play a crucial role in protection against neoplastic disease. The purpose of this study is to investigate a critical balance between free radical activity and the antioxidant defense system in carcinogenesis associated with UC, using a model of experimental colitis induced in mice by dextran sulfate sodium (DSS) treatment.


METHODS
Chronic colitis was induced by feeding the mice for 7 days with 4% DSS, followed by drinking water alone for the subsequent 14 days. Animals were sacrificed after one, two, three, or four cycles of DSS administration. Development of dysplastic epithelium and invasive carcinoma was histologically examined. Lipid peroxide level was estimated by measuring malondialdehyde (MDA) content. Alterations in MDA content and superoxide dismutase (SOD) activity in colonic tissues together with production of serum tumor necrosis factor (TNF)-alpha were determined.


RESULTS
Colonic neoplasms including dysplastic epithelium and invasive carcinoma developed in 28.6 and 25.0% of the animals at the end of the third and fourth cycles, respectively. In accordance with elevation of serum TNF-alpha level, there was a substantial increase in MDA in the colonic mucosa, while tissue SOD activity tended to be suppressed during the DSS treatment periods. Dysplastic epithelium and invasive carcinoma revealed significantly lower SOD levels compared with colonic colitis, although MDA levels were not statistically different among these colonic diseases.


CONCLUSIONS
The results obtained in this experimental model suggest that an impaired antioxidant defense system might be critical for cancer development associated with UC.
Korenaga
Daisuke
D
Department of General Surgery, Fukuoka Dental College Hospital, Fukuoka 814-0193, Japan. korenaga@college.fdcnet.ac.jp
Takesue
Fumio
F
Kido
Kazuaki
K
Yasuda
Mitsuhiro
M
Inutsuka
Sadaaki
S
Honda
Masayuki
M
Nagahama
Shunichi
S
D000818:Animals; D000925:Anticoagulants; D000975:Antioxidants / Q000378:metabolism* / Q000494:pharmacology; D001205:Ascorbic Acid / Q000378:metabolism / Q000494:pharmacology; D002908:Chronic Disease; D003092:Colitis / Q000139:chemically induced / Q000150:complications / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control; D016264:Dextran Sulfate; D005260:Female; D005609:Free Radicals / Q000378:metabolism; D007413:Intestinal Mucosa / Q000201:enzymology; D008054:Lipid Peroxides / Q000378:metabolism; D008315:Malondialdehyde / Q000032:analysis; D051379:Mice; D008815:Mice, Inbred Strains; D013482:Superoxide Dismutase / Q000032:analysis / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000925:Anticoagulants; D000975:Antioxidants; D005609:Free Radicals; D008054:Lipid Peroxides; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D016264:Dextran Sulfate; D013482:Superoxide Dismutase; D001205:Ascorbic Acid